WorldWideScience

Sample records for actinium 227 target

  1. Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes.

    Science.gov (United States)

    Radchenko, V; Engle, J W; Wilson, J J; Maassen, J R; Nortier, F M; Taylor, W A; Birnbaum, E R; Hudston, L A; John, K D; Fassbender, M E

    2015-02-06

    Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% β(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 μCi). Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Synthesis and Characterization of the Actinium Aquo Ion.

    Science.gov (United States)

    Ferrier, Maryline G; Stein, Benjamin W; Batista, Enrique R; Berg, John M; Birnbaum, Eva R; Engle, Jonathan W; John, Kevin D; Kozimor, Stosh A; Lezama Pacheco, Juan S; Redman, Lindsay N

    2017-03-22

    Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H 2 O) x 3+ ) is critical for current efforts to develop 225 Ac [ t 1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity, many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227 Ac [ t 1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the Ac III cation with an Ac-O H2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that Ac III was coordinated by 9 water molecules with Ac-O H2O distances ranging from 2.61 to 2.76 Å. The data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large Ac III coordination numbers and long Ac-O H2O bond distances.

  3. An eighteen-membered macrocyclic ligand for actinium-225 targeted alpha therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thiele, Nikki A.; MacMillan, Samantha N.; Wilson, Justin J. [Cornell Univ., Ithaca, NY (United States). Chemistry and Chemical Biology; Brown, Victoria; Jermilova, Una; Ramogida, Caterina F.; Robertson, Andrew K.H.; Schaffer, Paul; Radchenko, Valery [TRIUMF, Vancouver, BC (Canada). Life Science Div.; Kelly, James M.; Amor-Coarasa, Alejandro; Nikolopoulou, Anastasia; Ponnala, Shashikanth; Williams, Clarence Jr.; Babich, John W. [Radiology, Weill Cornell Medicine, New York, NY (United States); Rodriguez-Rodriguez, Cristina [British Columbia Univ., Vancouver, BC (Canada). Dept. of Physics and Astronomy and Centre for Comparative Medicine

    2017-11-13

    The 18-membered macrocycle H{sub 2}macropa was investigated for {sup 225}Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all {sup 225}Ac (26 kBq) in 5 min at RT. [{sup 225}Ac(macropa)]{sup +} remained intact over 7 to 8 days when challenged with either excess La{sup 3+} ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled {sup 225}Ac in just minutes at RT, and macropa-Tmab retained >99 % of its {sup 225}Ac in human serum after 7 days. In LNCaP xenograft mice, {sup 225}Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free {sup 225}Ac over 96 h. These findings establish macropa to be a highly promising ligand for {sup 225}Ac chelation that will facilitate the clinical development of {sup 225}Ac TAT for the treatment of soft-tissue metastases. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. 40 CFR 745.227 - Work practice standards for conducting lead-based paint activities: target housing and child...

    Science.gov (United States)

    2010-07-01

    ... lead-based paint activities: target housing and child-occupied facilities. 745.227 Section 745.227... PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.227 Work practice standards for conducting lead-based paint activities: target housing and child-occupied facilities...

  5. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, James T.; Nolen, Jerry; Vandergrift, George; Gomes, Itacil; Kroc, Tom; Horwitz, Phil; McAlister, Dan; Bowers, Del; Sullivan, Vivian; Greene, John

    2011-12-30

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces {approx}100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 Ge

  6. Targeted alpha therapy using a novel CD70 targeted thorium-227 conjugate in in vitro and in vivo models of renal cell carcinoma.

    Science.gov (United States)

    Hagemann, Urs B; Mihaylova, Dessislava; Uran, Steinar R; Borrebaek, Joergen; Grant, Derek; Bjerke, Roger M; Karlsson, Jenny; Cuthbertson, Alan S

    2017-08-22

    The cell surface receptor CD70 has been previously reported as a promising target for B-cell lymphomas and several solid cancers including renal cell carcinoma. We describe herein the characterization and efficacy of a novel CD70 targeted thorium-227 conjugate (CD70-TTC) comprising the combination of the three components, a CD70 targeting antibody, a chelator moiety and the short-range, high-energy alpha-emitting radionuclide thorium-227 ((227)Th). In vitro analysis demonstrated that the CD70-TTC retained binding affinity to its target and displayed potent and specific cytotoxicity compared to an isotype control-TTC. A biodistribution study in subcutaneous tumor-bearing nude mice using the human renal cell carcinoma cell line 786-O demonstrated significant uptake and retention with 122 ± 42% of the injected dose of (227)Th per gram (% ID/g) remaining in the tumor seven days post dose administration compared to only 3% ID/g for the isotype control-TTC. Tumor accumulation correlated with a dose dependent and statistically significant inhibition in tumor growth compared to vehicle and isotype control-TTC groups at radioactivity doses as low as 50 kBq/kg. The CD70-TTC was well tolerated as evidenced by only modest changes in hematology and normal gain in body weight of the mice. To our knowledge, this is the first report describing molecular targeting of CD70 expressing tumors using a targeted alpha-therapy (TAT).

  7. Synthesis and Characterization of the Actinium Aquo Ion

    OpenAIRE

    Maryline G. Ferrier; Benjamin W. Stein; Enrique R. Batista; John M. Berg; Eva R. Birnbaum; Jonathan W. Engle; Kevin D. John; Stosh A. Kozimor; Juan S. Lezama Pacheco; Lindsay N. Redman

    2017-01-01

    Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H2O) x 3+) is critical for current ef...

  8. In-source laser spectroscopy developments at TRILIS-towards spectroscopy on actinium and scandium

    Energy Technology Data Exchange (ETDEWEB)

    Raeder, Sebastian, E-mail: raeder@triumf.ca; Dombsky, Marik; Heggen, Henning; Lassen, Jens; Quenzel, Thomas [TRIUMF, Canada' s National Laboratory for Nuclear and Particle Physics (Canada); Sjoedin, Marica [GANIL (France); Teigelhoefer, Andrea [TRIUMF, Canada' s National Laboratory for Nuclear and Particle Physics (Canada); Wendt, Klaus [Johannes Gutenberg-Universitaet Mainz, Institut fuer Physik (Germany)

    2013-04-15

    Resonance Ionization Laser Ion Sources (RILIS) have become a versatile tool for production and study of exotic nuclides at Isotope Separator On-Line (ISOL) facilities such as ISAC at TRIUMF. The recent development and addition of a grating tuned spectroscopy laser to the TRIUMF RILIS solid state laser system allows for wide range spectral scans to investigate atomic structures on short lived isotopes, e.g., those from the element actinium, produced in uranium targets at ISAC. In addition, development of new and improved laser ionization schemes for rare isotope production at ISAC is ongoing. Here spectroscopic studies on bound states, Rydberg states and autoionizing (AI) resonances on scandium using the existing off-line capabilities are reported. These results allowed to identify a suitable ionization scheme for scandium via excitation into an autoionizing state at 58,104 cm{sup - 1} which has subsequently been used for ionization of on-line produced exotic scandium isotopes.

  9. Development of separation technology for the removal of radium-223 from targeted thorium conjugate formulations. Part I: purification of decayed thorium-227 on cation exchange columns.

    Science.gov (United States)

    Frenvik, Janne Olsen; Dyrstad, Knut; Kristensen, Solveig; Ryan, Olav B

    2017-02-01

    Targeted thorium conjugates (TTCs) are being explored as a potential future platform for specific tumor targeting pharmaceuticals. In TTCs, the alpha emitting radionuclide thorium-227 ((227)Th) with a half-life of 18.697 d is labeled to targeting moieties, such as monoclonal antibodies (mAbs). The amount of daughter nuclide radium-223 ((223)Ra, t1/2 = 11.435 d) will increase during manufacture and distribution, and so a technology for purification is required to assure an acceptable level of (223)Ra is administrated to the patient. Since (223)Ra is the only progeny of (227)Th with a long half-life (days), the progenies of (223)Ra will have a very limited stay in the formulation once (223)Ra is removed. The focus in this study has, therefore, been on the removal of (223)Ra. In this study, the sorption and separation of (223)Ra (radium(II)) and (227)Th (thorium(IV)) on cation exchange columns has been evaluated as a purification method of decayed (227)Th (i.e. prior to radiolabelling of a mAb and formation of TTC). The goal is to minimize the sorption of (227)Th and maximize the sorption of (223)Ra. Statistical experimental design with formulation and process parameters, including buffered formulations comprising citrate and acetate, at various concentrations and pH, presence of free radical scavenger and chelator, and resin amount have been evaluated for impact on the purification process. The studies have been interpreted by the aid of multivariate data analysis. The correlations between design of experimental variables and sorption are summarized by regression models. The predictive accuracy of radionuclide sorption was given by standard deviation and 95% confidence intervals originating from statistical cross validation. Experimental results and statistical models for citrate-buffered formulations verified reproducible and acceptable sorption levels of (223)Ra and (227)Th under selected conditions. For acetate-buffered formulations, prediction of (227)Th

  10. LaPO4 Nanoparticles Doped with Actinium-225 that Partially Sequester Daughter Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Woodward, Jonathan [ORNL; Kennel, Steve J [ORNL; Stucnkey, Alan [University of Tennessee, Knoxville (UTK); Osborne, Dustin [University of Tennessee, Knoxville (UTK); Wall, Jonathan [University of Tennessee, Knoxville (UTK); Rondinone, Adam Justin [ORNL; Standaert, Robert F [ORNL; Mirzadeh, Saed [ORNL

    2011-01-01

    Nanoscale materials have been envisioned as carriers for various therapeutic drugs, including radioisotopes. Inorganic nanoparticles (NPs) are particularly appealing vehicles for targeted radiotherapy because they can package several radioactive atoms into a single carrier and can potentially retain daughter radioisotopes produced by in vivo generators such as actinium -225 (225Ac, t1/2=10 d). Decay of this radioisotope to stable bismuth-209 proceeds through a chain of short-lived daughters accompanied by the emission of four -particles that release >27 MeV of energy. The challenge in realizing the enhanced cytotoxic potential of in vivo generators lies in retaining the daughter nuclei at the therapy site. When 225Ac is attached to targeting agents via standard chelate conjugation methods, all of the daughter radionuclides are released after the initial -decay occurs. In this work, 225Ac was incorporated into lanthanum phosphate NPs to determine whether the radioisotope and its daughters would be retained within the dense mineral lattice. Further, the 225Ac-doped NPs were conjugated to the monoclonal antibody mAb 201B, which targets mouse lung endothelium through the vasculature, to ascertain the targeting efficacy and in vivo retention of radioisotopes. Standard biodistribution techniques and microSPECT/CT imaging of 225Ac as well as the daughter radioisotopes showed that the NPs accumulated rapidly in mouse lung after intravenous injection. By showing that excess, competing, uncoupled antibodies or NPs coupled to control mAbs are deposited primarily in the liver and spleen, specific targeting of NP-mAb 201B conjugates was demonstrated. Biodistribution analysis showed that ~30% of the total injected dose of La(225Ac)PO4 NPs accumulated in mouse lungs 1 h post-injection yielding a value of % ID/g >200. Furthermore, after 24 h, 80% of the 213Bi daughter produced from 225Ac decay was retained within the target organ and 213Bi retention increased to ~87% at 120 h. In

  11. Fractionated therapy of HER2-expressing breast and ovarian cancer xenografts in mice with targeted alpha emitting 227Th-DOTA-p-benzyl-trastuzumab.

    Directory of Open Access Journals (Sweden)

    Helen Heyerdahl

    Full Text Available BACKGROUND: The aim of this study was to investigate therapeutic efficacy and normal tissue toxicity of single dosage and fractionated targeted alpha therapy (TAT in mice with HER2-expressing breast and ovarian cancer xenografts using the low dose rate radioimmunoconjugate (227Th-DOTA-p-benzyl-trastuzumab. METHODOLOGY/PRINCIPAL FINDINGS: Nude mice carrying HER2-overexpressing subcutaneous SKOV-3 or SKBR-3 xenografts were treated with 1000 kBq/kg (227Th-trastuzumab as single injection or four injections of 250 kBq/kg with intervals of 4-5 days, 2 weeks, or 4 weeks. Control animals were treated with normal saline or unlabeled trastuzumab. In SKOV-3 xenografts tumor growth to 10-fold size was delayed (p<0.01 and survival with tumor diameter less than 16 mm was prolonged (p<0.05 in all TAT groups compared to the control groups. No statistically significant differences were seen among the treated groups. In SKBR-3 xenografts tumor growth to 10-fold size was delayed in the single injection and 4-5 days interval groups (p<0.001 and all except the 4 weeks interval TAT group showed improved survival to the control groups (p<0.05. Toxicity was assessed by blood cell counts, clinical chemistry measurements and body weight. Transient reduction in white blood cells was seen for the single injection and 4-5 days interval groups (p<0.05. No significant changes were seen in red blood cells, platelets or clinical chemistry parameters. Survival without life threatening loss of body weight was significantly prolonged in 4 weeks interval group compared to single injection group (p<0.05 for SKOV-3 animals and in 2 weeks interval group compared with the 4-5 days interval groups (p<0.05 for SKBR-3 animals. CONCLUSIONS/SIGNIFICANCE: The same concentration of radioactivity split into several fractions may improve toxicity of (227Th-radioimmunotherapy while the therapeutic effect is maintained. Thus, it might be possible to increase the cumulative absorbed radiation dose

  12. Developments towards in-gas-jet laser spectroscopy studies of actinium isotopes at LISOL

    Energy Technology Data Exchange (ETDEWEB)

    Raeder, S., E-mail: s.raeder@gsi.de [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Helmholtz-Institut Mainz, 55128 Mainz (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Bastin, B. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); Block, M. [Helmholtz-Institut Mainz, 55128 Mainz (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Institut für Kernchemie, Johannes Gutenberg Universität, 55128 Mainz (Germany); Creemers, P. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Delahaye, P. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); Ferrer, R. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Fléchard, X. [LPC Caen, ENSICAEN, Université de Caen, CNRS/IN2P3, Caen (France); Franchoo, S. [Institute de Physique Nucléaire (IPN) d’Orsay, 91406 Orsay, Cedex (France); Ghys, L. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); SCK-CEN, Belgian Nuclear Research Center, Boeretang 200, 2400 Mol (Belgium); Gaffney, L.P.; Granados, C. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Heinke, R. [Institut für Physik, Johannes Gutenberg Universität, 55128 Mainz (Germany); Hijazi, L. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); and others

    2016-06-01

    To study exotic nuclides at the borders of stability with laser ionization and spectroscopy techniques, highest efficiencies in combination with a high spectral resolution are required. These usually opposing requirements are reconciled by applying the in-gas-laser ionization and spectroscopy (IGLIS) technique in the supersonic gas jet produced by a de Laval nozzle installed at the exit of the stopping gas cell. Carrying out laser ionization in the low-temperature and low density supersonic gas jet eliminates pressure broadening, which will significantly improve the spectral resolution. This article presents the required modifications at the Leuven Isotope Separator On-Line (LISOL) facility that are needed for the first on-line studies of in-gas-jet laser spectroscopy. Different geometries for the gas outlet and extraction ion guides have been tested for their performance regarding the acceptance of laser ionized species as well as for their differential pumping capacities. The specifications and performance of the temporarily installed high repetition rate laser system, including a narrow bandwidth injection-locked Ti:sapphire laser, are discussed and first preliminary results on neutron-deficient actinium isotopes are presented indicating the high capability of this novel technique.

  13. AAS 227: Day 2

    Science.gov (United States)

    Kohler, Susanna

    2016-01-01

    tests of GR, and performing predictive GRMHD simulations hydrodynamics simulations that include magnetic fields and full GR treatment. Ozel pointed out that one of the recent theoretical advancements in GRMHD simulations is harnessing the power of GPUs to render images in simulations; check out the tweet below for the awesome video she showed us!Watch C. Chan manipulate black hole simulation with hand motions https://t.co/O5BgaltYAu (more on the code: https://t.co/9GC46ReMGs) #aas227 Sarah Scoles (@ScolesSarah) January 6, 2016Deployment of the full EHT array is planned for early 2017, and theyve already got 10 targets selected black holes that are near enough and large enough that the EHT should be able to image their shadows. I, for one, cant wait to see the first results!Grad School and Postdocs as a Means to a Job (by Meredith Rawls)This morning session was presented by Karen Kelsky of The Professor Is In. She presented a very practical overview of the advice in her book (which this job-searching Astrobiter highly recommends). Her target audience is postdocs and graduate students who are finishing their PhDs and applying for tenure-track jobs. Karens background is in the social sciences, but she has worked with many scientists and her expertise easily transferred. Much of her writing advice also applies for undergraduates who are writing research statements and proposals to apply to graduate school. For example:What not to do, with @ProfessorIsIn #aas227 pic.twitter.com/afGAsSuPwN Meredith Rawls (@merrdiff) January 6, 2016One of Karens main takeaways is that academia is not automatically good preparation for a job search. Writing documents like cover letters, resumes, and research statements will be harder and take more time than you think, and it is important to make them top-notch. Karen was also surprised that the majority of professional astronomers at the AAS meeting carry backpacks, because she typically advises against bringing a backpack to a job interview or

  14. The release of dissolved actinium to the ocean: A global comparison of different end-members

    Science.gov (United States)

    Geibert, W.; Charette, M.; Kim, G.; Moore, W.S.; Street, J.; Young, M.; Paytan, A.

    2008-01-01

    The measurement of short-lived 223Ra often involves a second measurement for supported activities, which represents 227Ac in the sample. Here we exploit this fact, presenting a set of 284 values on the oceanic distribution of 227Ac, which was collected when analyzing water samples for short-lived radium isotopes by the radium delayed coincidence counting system. The present work compiles 227Ac data from coastal regions all over the northern hemisphere, including values from ground water, from estuaries and lagoons, and from marine end-members. Deep-sea samples from a continental slope off Puerto Rico and from an active vent site near Hawaii complete the overview of 227Ac near its potential sources. The average 227Ac activities of nearshore marine end-members range from 0.4??dpm m- 3 at the Gulf of Mexico to 3.0??dpm m- 3 in the coastal waters of the Korean Strait. In analogy to 228Ra, we find the extension of adjacent shelf regions to play a substantial role for 227Ac activities, although less pronounced than for radium, due to its weaker shelf source. Based on previously published values, we calculate an open ocean 227Ac inventory of 1.35 * 1018??dpm 227Acex in the ocean, which corresponds to 37??moles, or 8.4??kg. This implies a flux of 127??dpm m-2 y- 1 from the deep-sea floor. For the shelf regions, we obtain a global inventory of 227Ac of 4.5 * 1015??dpm, which cannot be converted directly into a flux value, as the regional loss term of 227Ac to the open ocean would have to be included. Ac has so far been considered to behave similarly to Ra in the marine environment, with the exception of a strong Ac source in the deep-sea due to 231Paex. Here, we present evidence of geochemical differences between Ac, which is retained in a warm vent system, and Ra, which is readily released [Moore, W.S., Ussler, W. and Paull, C.K., 2008-this issue. Short-lived radium isotopes in the Hawaiian margin: Evidence for large fluid fluxes through the Puna Ridge. Marine Chemistry

  15. Proposition 227: What Now?

    Science.gov (United States)

    Ward, Ben

    1998-01-01

    Provides background on and discusses the significance of Proposition 227, the California ballot initiative designed to reform the state's bilingual-education program that was approved by voters in 1998. Reactions to its approval by California voters are provided by Ron Unz, Stephen Krashen, and Mauro Mujica. (Author/VWL)

  16. AAS 227: Day 1

    Science.gov (United States)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or at astrobites.com, or catch ourlive-tweeted updates from the @astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto have so many people tell us that they already know about and useastrobites, and we were excited to introduce a new cohort of students at AAS to astrobites for the first time.Tuesday morning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended today.Opening Address (by Becky Smethurst)The President of the AAS, aka our fearless leader Meg Urry kicked off the meeting this morning at the purely coffee powered hour of 8am this morning. She spoke about the importance of young astronomers at the meeting (heres looking at you reader!) and also the importance of the new Working Group for Accessibility and Disabilities (aka WGAD pronounced like wicked) at the AAS. The Society has made extra effort this year to make the conference accessible to all,a message which was very well received by everyone in attendance.Kavli Lecture: New Horizons Alan Stern (by Becky Smethurst)We were definitely spoilt with the first Plenary lecture at this years conference Alan Stern gave us a a review of the New Horizons mission of the Pluto Fly By (astrobites covered the mission back in July with this post). We were treated to beautiful images, wonderful results and a foray into geology.Before (Hubble) and after #NewHorizons. #thatisall #science #astro alanstern #aas227 pic.twitter.com/kkMt6RsSIR Science News (@topsciencething) January 5, 2016Some awesome facts from the lecture that blew my mind:New Horizons is now 2AU (!) beyond Pluto

  17. AAS 227: Day 3

    Science.gov (United States)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 3 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Henry Norris Russell Lecture: Viewing the Universe with Infrared Eyes: The Spitzer Space Telescope (by Erika Nesvold)The Henry Norris Russell Award is the highest honor given by the AAS, for a lifetime of eminence in astronomy research. This years award went to Giovanni Fazio of the Harvard-Smithsonian Center for Astrophysics. Fazio became a leader in gamma ray astronomy before switching mid-career to the study of infrared astronomy, and he gave his award lecture on the latter subject, specifically on the Spitzer Space Telescope, one of the most successful infrared telescopes of all time.Artists rendering of the Spitzer space telescope. [NASA/JPL-Caltech]Spitzer has been operating for more than twelve years, and has resulted in over six thousand papers in refereed journals in that time. The telescope sits in an Earth-trailing orbit around the Sun, and is now farther from the Earth (1.4 AU) than the Earth is from the Sun. Fazio gave the audience a fascinating overview of the science done by Spitzer over more than a decade. One of the most productive areas of research for Spitzer is the study of exoplanets, which hadnt even been discovered when the Spitzer Telescope was first conceived. Spitzers high sensitivity and ability to observe exoplanets over

  18. 40 CFR 227.11 - Containerized wastes.

    Science.gov (United States)

    2010-07-01

    ... 227.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Environmental Impact § 227.11... or leak on impact or shortly thereafter must meet the appropriate requirements of §§ 227.6, 227.7...

  19. AAS 227: Day 4

    Science.gov (United States)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 4 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Helen B. Warner Prize: Origins of Structure in Planetary Systems (by Erika Nesvold)Another excellent prize lecture started off todays sessions. The Helen B. Warner Prize is awarded for achievement in observational or theoretical astrophysics by a young researcher (no more than eight years after their Ph.D.). This years Warner Prize was presented to Ruth Murray-Clay of UC Santa Barbara. For her award lecture, Murray-Clay told us all about planetary system architecture: the number, masses, and orbits of planets in a given system.Ruth Murray-Clay [photo from http://web.physics.ucsb.edu/ ~murray/biocv.html]The underlying question motivating this type of research is: How rare is the Solar System? In other words, how likely is it that a given planetary system will have rocky planets close to their star, gas giants farther out, and ice giants at the outer reaches of the system? Answering this question will help us solve the physics problem of how and where planets form, and will also help us on our search for other planets like Earth.The data on exoplanet population from transit and radial velocity observations and from direct imaging tell us that our Solar System is not common (many systems we observe have much more eccentric gas giants), but that doesnt

  20. Nuclear Data Sheets for A = 227

    Energy Technology Data Exchange (ETDEWEB)

    Kondev, Filip [ANL, Argonne, IL (United States); McCutchan, Elizabeth [NNDC, BNL, Upton, NY (United States); Singh, Balraj, E-mail: balraj@mcmaster.ca [McMaster Univ., Hamilton (Canada); Tuli, Jagdish [NNDC, BNL, Upton, NY (United States)

    2016-02-15

    The evaluated spectroscopic data are presented for ten known nuclides of mass 227 (Po, At, Rn, Fr, Ra, Ac, Th, Pa, U, Np). For {sup 227}Po, {sup 227}At, {sup 227}Rn, {sup 227}Pa, {sup 227}U and {sup 227}Np nuclei, only the ground-state information is available. Their decay characteristics are mostly unknown. Levels in {sup 227}Fr are known only from the decay of {sup 227}Rn to {sup 227}Fr. This decay scheme at present cannot be normalized to deduce γ intensities per 100 decays due to lack of knowledge about multipolarities of many low-energy transitions. The levels in {sup 227}Ra, {sup 227}Ac and {sup 227}Th are known from several decays and reactions, including particle-transfer data for {sup 227}Ra and {sup 227}Ac. The decay scheme of {sup 227}Ra to {sup 227}Ac was last studied in 1971 using small Ge detectors. Improved γ-ray intensity data need to be obtained with a better γ-detection system. The datasets for {sup 227}Ac have undergone extensive revisions, including detailed data for 231Pa α decay from 1986BaYK report, and single-proton transfer data from 1986MaYU thesis. High-spin (J>13/2 or so) structures are known only for 227Th. Level lifetime data are quite scarce for all the nuclides in this mass chain, thus limiting the knowledge of reduced transition probabilities. Band structures for {sup 227}Fr, {sup 227}Ra, {sup 227}Ac and {sup 227}Th are known in detail, together with evidence of weak octupole deformation and consequent parity-doublet structures. This evaluation was carried out as part of a joint IAEA-ICTP workshop for Nuclear Structure and Decay Data, organized and hosted by the IAEA, Vienna and ICTP, Trieste, March 24–28, 2014. The evaluation work was coordinated by B. Singh (McMaster). This work supersedes previous A=227 evaluation (2001Br31) published by E. Browne which covered literature before May 2001.

  1. 22 CFR 227.405 - Penalty procedures.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Penalty procedures. 227.405 Section 227.405 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NEW RESTRICTIONS ON LOBBYING Penalties and Enforcement § 227.405 Penalty procedures. Agencies shall impose and collect civil penalties pursuant to the...

  2. 49 CFR 238.227 - Suspension system.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Suspension system. 238.227 Section 238.227 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Equipment § 238.227 Suspension system. On or after November 8, 1999— (a) All passenger equipment shall...

  3. 48 CFR 227.7103-9 - Copyright.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Copyright. 227.7103-9..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7103-9 Copyright. (a) Copyright license. (1) The clause at 252.227-7013, Rights in Technical Data...

  4. 7 CFR 1951.227 - Protective advances.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Protective advances. 1951.227 Section 1951.227... Programs Loans and Grants § 1951.227 Protective advances. The State Director is authorized to approve... protect its lien or security. The State Director must determine that authorizing a protective advance is...

  5. 7 CFR 227.3 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Administration. 227.3 Section 227.3 Agriculture... CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.3 Administration. (a) Within the Department, FNS shall act on behalf of the Department in the administration of the Program. (b...

  6. 20 CFR 227.1 - Introduction.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Introduction. 227.1 Section 227.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT COMPUTING SUPPLEMENTAL ANNUITIES § 227.1 Introduction. This part explains how to compute a supplemental annuity. A supplemental...

  7. Canadair CL-227 Remotely Piloted Vehicle

    Science.gov (United States)

    Clark, Andrew S.

    1983-08-01

    The Canadair CL-227 is a rotary winged Remotely Piloted Vehicle (RPV) intended initially as the air-vehicle for a medium range battlefield surveillance and target acquisition system. The concept on which this vehicle is based brings together in-house expertise as a designer and manufacturer of surveillance drones (AN-USD-50l -MIDGE-) with experience in rigid rotor technology from the CL-84 tilt wing VTOL program. The vehicle is essentially modular in design with a power module containing the engine, fuel and related systems, a rotor module containing the two counter-rotating rotors and control actuators, and a control module containing the autopilot, data link and sensor system. The vehicle is a true RPV (as opposed to a drone) as it is flown in real time by an operator on the ground and requires relatively little skill to pilot.

  8. 227

    African Journals Online (AJOL)

    2003-05-01

    , the circumstances surrounding the injuries or ... to infected blood have resulted in hepatitis B or C virus and. HIV infections among health care ... may be as high as l2-. 27% among dentists and oral surgeons(3). Studies have ...

  9. 48 CFR 227.7105-1 - General.

    Science.gov (United States)

    2010-10-01

    ... 227.7105-1 General. (a) Existing works include motion pictures, television recordings, video... literary works; pantomimes and choreographic works; pictorial, graphic, and sculptural works; and works of...

  10. 48 CFR 227.7201 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7201 Definitions. (a) As used in this subpart, unless... subpart are defined in the clause at 252.227-7014, Rights in Noncommercial Computer Software and...

  11. 7 CFR 1280.227 - Confidentiality.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidentiality. 1280.227 Section 1280.227 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Confidentiality. All information obtained from books, records, or reports under the Act, this subpart, and the...

  12. 44 CFR 206.227 - Snow assistance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Snow assistance. 206.227 Section 206.227 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Snow assistance. Emergency or major disaster declarations based on snow or blizzard conditions will be...

  13. 7 CFR 58.227 - Sampling device.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION, GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General... 7 Agriculture 3 2010-01-01 2010-01-01 false Sampling device. 58.227 Section 58.227 Agriculture...

  14. 27 CFR 44.227 - Customs procedure.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Customs procedure. 44.227..., WITHOUT PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Drawback of Tax § 44.227 Customs procedure. The customs... having inspected the articles and supervised the lading thereof on the export carrier, the customs...

  15. 49 CFR 227.115 - Hearing protectors.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Hearing protectors. 227.115 Section 227.115 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating...

  16. 40 CFR 227.5 - Prohibited materials.

    Science.gov (United States)

    2010-07-01

    ... 227.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Environmental Impact § 227.5... environmental impact criteria of this subpart B; (d) Persistent inert synthetic or natural materials which may...

  17. Dicty_cDB: VHP227 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VH (Link to library) VHP227 (Link to dictyBase) - - - - VHP227P (Link to Original site) VHP227F 553 VHP...227Z 683 VHP227P 1216 - - Show VHP227 Library VH (Link to library) Clone ID VHP227 (Link... to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig - Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/VH/VHP...2-B/VHP227Q.Seq.d/ Representative seq. ID VHP227P (Link to... Original site) Representative DNA sequence >VHP227 (VHP227Q) /CSM/VH/VHP2-B/VHP227Q.Seq.d/ GAGAAAGCCTCCGTAA

  18. 30 CFR 22.7 - Specific requirements.

    Science.gov (United States)

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.7 Specific requirements. (a) Design. In the... mixtures, and by the general behavior of the equipment during the investigation. (b) Safety against...

  19. The nuclear structure of $^{227}$Fr

    CERN Document Server

    Kurcewicz, W; Gulda, K; Aas, A J; Billowes, J; García-Borge, M J; Burke, D G; Butler, P A; Cocks, J F C; Fogelberg, B; Freeman, S J; Jones, G D; Hagebø, E; Hoff, P; Hønsi, J; Lindroth, A; Løvhøiden, G; Mach, H; Martínez, T; Naumann, R A; Nybø, K; Nyman, G H; Ravn, H L; Rubio, B; Simpson, J; Smith, A G; Smith, J F; Steffensen, K; Taín, J L; Tengblad, O; Thorsteinsen, T F

    1997-01-01

    The $\\gamma$-rays following the $\\beta^{-}$-decay of $^{227}$Rn have been investigated by means of $\\gamma$-ray singles and $\\gamma\\gamma$-coincidence measurements using an array of 12 Compton-suppressed Ge detectors. The fast timing $\\beta\\gamma\\gamma$(t) method has been used to measure six level lifetimes. Multipolarities of 32 transitions in $^{227}$Fr have been established by measuring conversion electrons with a mini--orange electron spectrometer. Most of the observed transitions have been placed in a level scheme comprising 38 excited states of $^{227}$Fr. The low-lying levels are interpreted in terms of seven rotational bands. The observed E1 strengths for two transitions connecting the K$^{\\pi}$=3/2 bands are consistent with the transitional character of $^{227}$Fr, and confirm the presence of octupole correlations in this nucleus.

  20. 48 CFR 227.7203-1 - Policy.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-1 Policy. (a) DoD policy is to acquire only the computer software and computer software documentation, and the rights in such software or documentation, necessary...

  1. 48 CFR 227.7202-1 - Policy.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7202-1 Policy. (a) Commercial computer software or commercial computer software documentation shall be acquired under the licenses customarily provided to the public...

  2. 48 CFR 227.7203-9 - Copyright.

    Science.gov (United States)

    2010-10-01

    ... Software and Computer Software Documentation 227.7203-9 Copyright. (a) Copyright license. (1) The clause at... computer software documentation will be negotiated, negotiate the extent of the copyright license... computer software documentation, do not negotiate a copyright license that provides less rights than the...

  3. 7 CFR 227.5 - Program funding.

    Science.gov (United States)

    2010-01-01

    ... CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.5 Program funding. (a... Education. (b) First fiscal year participation—(1) Assessment and planning grant. A portion of the total... administrative costs shall consist of an amount equal to 50 cents per child enrolled in schools and institutions...

  4. 7 CFR 227.2 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.2 Definitions. (a... section 17 of the National School Lunch Act, as amended. (c) Child Nutrition Programs means any or all of... of the Child Nutrition Act of 1966, as amended. (n) School means: (1) An educational unit of high...

  5. 36 CFR 223.227 - Sale advertisement.

    Science.gov (United States)

    2010-07-01

    ... advertisement. (a) The Forest Service shall advertise any special forest products sales with an appraised value... products without advertisement, or advertise a special forest products sale for a period less than 30 days... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Sale advertisement. 223.227...

  6. 12 CFR 227.25 - Unfair balance computation method.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Unfair balance computation method. 227.25 Section 227.25 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL... Practices Rule § 227.25 Unfair balance computation method. (a) General rule. Except as provided in paragraph...

  7. 48 CFR 1552.227-76 - Project employee confidentiality agreement.

    Science.gov (United States)

    2010-10-01

    ... confidentiality agreement. 1552.227-76 Section 1552.227-76 Federal Acquisition Regulations System ENVIRONMENTAL... Clauses 1552.227-76 Project employee confidentiality agreement. As prescribed in 1527.409, insert the following clause: Project Employee Confidentiality Agreement (MAY 1994) (a) The Contractor recognizes that...

  8. 22 CFR Appendix A to Part 227 - Certification Regarding Lobbying

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certification Regarding Lobbying A Appendix A to Part 227 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NEW RESTRICTIONS ON LOBBYING Pt. 227, App. A Appendix A to Part 227—Certification Regarding Lobbying Certification for Contracts...

  9. 22 CFR 227.300 - Professional and technical services.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Professional and technical services. 227.300 Section 227.300 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NEW RESTRICTIONS ON LOBBYING Activities by Other Than Own Employees § 227.300 Professional and technical services. (a) The prohibition on...

  10. 48 CFR 2453.227 - Patents, data, and copyrights.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Patents, data, and copyrights. 2453.227 Section 2453.227 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT CLAUSES AND FORMS FORMS Prescription of Forms 2453.227 Patents, data, and copyrights. ...

  11. 7 CFR 227.43 - Participation of adults.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM Miscellaneous § 227.43 Participation of adults. Nothing in this part shall prohibit a State or local educational agency from making... 7 Agriculture 4 2010-01-01 2010-01-01 false Participation of adults. 227.43 Section 227.43...

  12. 40 CFR 227.4 - Criteria for evaluating environmental impact.

    Science.gov (United States)

    2010-07-01

    ... impact. 227.4 Section 227.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Environmental Impact § 227.4 Criteria for evaluating environmental impact. This subpart B sets specific environmental...

  13. 48 CFR 227.7203-6 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-6 Contract clauses. (a)(1) Use the clause at 252.227-7014, Rights in Noncommercial Computer Software and Noncommercial Computer Software Documentation, in...

  14. 48 CFR 227.7103-6 - Contract clauses.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data... software or computer software documentation (see 227.72), commercial items (see 227.7102-3), existing works... Software Previously Delivered to the Government, in solicitations when the resulting contract will require...

  15. 48 CFR 227.7203-11 - Contractor procedures and records.

    Science.gov (United States)

    2010-10-01

    ... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-11 Contractor procedures and records. (a) The clause at 252.227-7014, Rights in Noncommercial Computer Software and Noncommercial...

  16. 48 CFR 227.7207 - Contractor data repositories.

    Science.gov (United States)

    2010-10-01

    ... SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7207 Contractor data repositories. Follow 227.7108 when it is in the Government's interests to have a data repository include computer software or to...

  17. 29 CFR 1952.227 - Changes to approved plans.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Changes to approved plans. 1952.227 Section 1952.227 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... plans. (a) Legislation. (1) On March 29, 1994, the Assistant Secretary approved Tennessee's revised...

  18. 40 CFR 86.227-94 - Test procedures; overview.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Test procedures; overview. 86.227-94 Section 86.227-94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... 1994 and Later Model Year Gasoline-Fueled New Light-Duty Vehicles, New Light-Duty Trucks and New Medium...

  19. 14 CFR 417.227 - Toxic release hazard analysis.

    Science.gov (United States)

    2010-01-01

    ... members of the public on land and on any waterborne vessels, populated offshore structures, and aircraft... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Toxic release hazard analysis. 417.227..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.227 Toxic release hazard...

  20. 49 CFR Appendix A to Part 227 - Noise Exposure Computation

    Science.gov (United States)

    2010-10-01

    ..., as given in Table A-1. 2. When the work day noise exposure is composed of two or more periods of... 49 Transportation 4 2010-10-01 2010-10-01 false Noise Exposure Computation A Appendix A to Part... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Pt. 227, App. A Appendix A to Part 227...

  1. 20 CFR 227.4 - Reduction for employer pension.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Reduction for employer pension. 227.4 Section... COMPUTING SUPPLEMENTAL ANNUITIES § 227.4 Reduction for employer pension. (a) General. The supplemental annuity for each month is reduced by the amount of any private pension the employee is receiving for that...

  2. 49 CFR 192.227 - Qualification of welders.

    Science.gov (United States)

    2010-10-01

    ... of welders. (a) Except as provided in paragraph (b) of this section, each welder must be qualified in accordance with section 6 of API 1104 (incorporated by reference, see § 192.7) or section IX of the ASME... 49 Transportation 3 2010-10-01 2010-10-01 false Qualification of welders. 192.227 Section 192.227...

  3. 12 CFR 22.7 - Forced placement of flood insurance.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Forced placement of flood insurance. 22.7... HAVING SPECIAL FLOOD HAZARDS § 22.7 Forced placement of flood insurance. If a bank, or a servicer acting... or mobile home and any personal property securing the designated loan is not covered by flood...

  4. 14 CFR 121.227 - Pressure cross-feed arrangements.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Pressure cross-feed arrangements. 121.227 Section 121.227 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS OPERATING...

  5. 48 CFR 52.227-3 - Patent Indemnity.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Patent Indemnity. 52.227-3... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 52.227-3 Patent Indemnity. As prescribed in 27.201-2(c)(1), insert the following clause: Patent Indemnity (APR 1984) (a) The...

  6. 40 CFR 98.227 - Records that must be retained.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Records that must be retained. 98.227... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.227 Records that must be retained. In addition to the information required by § 98.3(g), you must retain the records specified in...

  7. 27 CFR 41.227 - Change in location.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Change in location. 41.227 Section 41.227 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... 5230.5 for, and obtain, an amended permit. ...

  8. 14 CFR 16.227 - Standard of proof.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Standard of proof. 16.227 Section 16.227 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES OF... in the record and is in accordance with law. ...

  9. 22 CFR 227.600 - Semi-annual compilation.

    Science.gov (United States)

    2010-04-01

    ... Relations of the Senate and the Committee on Foreign Affairs of the House of Representatives or the... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Semi-annual compilation. 227.600 Section 227.600 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NEW RESTRICTIONS ON LOBBYING Agency Reports...

  10. 31 CFR 800.227 - U.S. national.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false U.S. national. 800.227 Section 800.227 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND...

  11. 48 CFR 227.7102-2 - Rights in technical data.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Rights in technical data... Technical Data 227.7102-2 Rights in technical data. (a) The clause at 252.227-7015, Technical Data—Commercial Items, provides the Government specific license rights in technical data pertaining to commercial...

  12. 48 CFR 227.7107 - Contracts for architect-engineer services.

    Science.gov (United States)

    2010-10-01

    ...-engineer services. 227.7107 Section 227.7107 Federal Acquisition Regulations System DEFENSE ACQUISITION... Rights in Technical Data 227.7107 Contracts for architect-engineer services. This section sets forth... of construction and architect-engineer services. ...

  13. 48 CFR 227.7202 - Commercial computer software and commercial computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7202 Commercial computer software and commercial computer software documentation. ... software and commercial computer software documentation. 227.7202 Section 227.7202 Federal Acquisition...

  14. 48 CFR 227.7203 - Noncommercial computer software and noncommercial computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203 Noncommercial computer software and noncommercial computer software documentation. ... software and noncommercial computer software documentation. 227.7203 Section 227.7203 Federal Acquisition...

  15. 48 CFR 227.7202-4 - Contract clause.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7202-4 Contract clause. A specific contract clause governing the Government's rights in commercial computer software or commercial computer software...

  16. 7 CFR 227.4 - Application and agreement.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.4 Application and agreement. After the initial fiscal year of participation each State agency desiring to take part in the...

  17. 7 CFR 227.1 - General purpose and scope.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.1 General purpose and scope. The purpose of these regulations is to implement section 19 of the Child Nutrition Act... child nutrition programs as a learning experience. ...

  18. 49 CFR 227.111 - Audiometric test requirements.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating Employees. § 227.111 Audiometric test requirements. (a) Audiometric tests shall be pure tone, air...

  19. 48 CFR 1352.227-70 - Rights in data, assignment of copyright.

    Science.gov (United States)

    2010-10-01

    ... of copyright. 1352.227-70 Section 1352.227-70 Federal Acquisition Regulations System DEPARTMENT OF....227-70 Rights in data, assignment of copyright. As prescribed in 48 CFR 1327.404-4(a), insert the following clause: Rights in Data, Assignment of Copyright (APR 2010) In accordance with 48 CFR 52.227-17...

  20. 48 CFR 227.7203-5 - Government rights.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-5 Government rights. The standard license rights in computer software that a licensor grants to the Government are unlimited rights, government purpose rights...

  1. 48 CFR 227.7200 - Scope of subpart.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7200 Scope of subpart. This subpart— (a) Prescribes policies and procedures for the acquisition of computer software and computer software documentation, and the...

  2. 49 CFR 227.117 - Hearing protector attenuation.

    Science.gov (United States)

    2010-10-01

    ... exposure to an 8-hour TWA of 90 decibels or lower, as required by § 227.115. (c) For employees who have...-weighted average of 85 decibels or lower. (d) The adequacy of hearing protector attenuation shall be re...

  3. 40 CFR 227.30 - High-level radioactive waste.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-level radioactive waste. 227.30...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste from...

  4. 40 CFR 227.31 - Applicable marine water quality criteria.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Applicable marine water quality... § 227.31 Applicable marine water quality criteria. Applicable marine water quality criteria means the criteria given for marine waters in the EPA publication “Quality Criteria for Water” as published in 1976...

  5. 48 CFR 1852.227-84 - Patent rights clauses.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Patent rights clauses. 1852... 1852.227-84 Patent rights clauses. The contracting officer shall insert the following provision as prescribed in 1827.303-70(e): Patent Rights Clauses (DEC 1989) This solicitation contains the patent rights...

  6. 48 CFR 227.676 - Foreign patent interchange agreements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Foreign patent interchange... SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Foreign License and Technical Assistance Agreements 227.676 Foreign patent interchange agreements. (a) Patent...

  7. 48 CFR 1852.227-70 - New technology.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true New technology. 1852.227-70... New technology. As prescribed in 1827.303-70(b), insert the following clause: New Technology (NOV 1998... administration of this New Technology clause within six months of conception and/or first actual reduction to...

  8. 48 CFR 227.7003 - Claims for copyright infringement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Claims for copyright... SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Infringement Claims, Licenses, and Assignments 227.7003 Claims for copyright infringement. The procedures set forth...

  9. 14 CFR 135.227 - Icing conditions: Operating limitations.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Icing conditions: Operating limitations... VFR/IFR Operating Limitations and Weather Requirements § 135.227 Icing conditions: Operating... to be free of frost, ice, or snow. (3) The certificate holder has an approved deicing/anti-icing...

  10. 48 CFR 227.7203-4 - License rights.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-4 License rights. (a) Grant of license. The Government obtains rights in computer software or computer software documentation, including a copyright...

  11. 7 CFR 227.35 - Responsibilities of State coordinator.

    Science.gov (United States)

    2010-01-01

    ... conducted with Federal or State funds, (h) Communication of needs and accomplishments of State nutrition... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator...

  12. 25 CFR 227.22 - Diligence and prevention of waste.

    Science.gov (United States)

    2010-04-01

    ... Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING Operations § 227.22 Diligence and... all damages to crops, buildings, and other improvements on the premises occasioned by the lessee's...

  13. 48 CFR 3452.227-72 - Advertising of awards.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Advertising of awards... Clauses 3452.227-72 Advertising of awards. As prescribed in 3427.472, insert the following clause in all solicitations and contracts other than purchase orders: Advertising of Awards (AUG 1987) The contractor agrees...

  14. 49 CFR 227.107 - Hearing conservation program.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating Employees. § 227.107 Hearing conservation program. (a) Consistent with the requirements of the... exposure shall be computed in accordance with the tables in appendix A of this part, and without regard to...

  15. 49 CFR 227.113 - Noise operational controls.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating Employees. § 227.113 Noise operational controls. (a) Railroads may use noise operational controls at any sound level to reduce exposures to levels below those required by Table A-1 of appendix A of...

  16. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken only with the following allowable gear and methods: (1) Hand harvest; (2) Spear; (3) Slurp gun; (4...

  17. 48 CFR 227.7103-17 - Overseas contracts with foreign sources.

    Science.gov (United States)

    2010-10-01

    ... COPYRIGHTS Rights in Technical Data 227.7103-17 Overseas contracts with foreign sources. (a) The clause at 252.227-7032, Rights in Technical Data and Computer Software (Foreign), may be used in contracts with...

  18. 48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

    Science.gov (United States)

    2010-10-01

    ... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Commercial computer software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL...

  19. 22 CFR Appendix B to Part 227 - Disclosure Form To Report Lobbying

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Disclosure Form To Report Lobbying B Appendix B to Part 227 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NEW RESTRICTIONS ON LOBBYING Pt. 227, App. B Appendix B to Part 227—Disclosure Form To Report Lobbying EC06OC91.012 EC06OC91.013...

  20. 40 CFR 227.16 - Basis for determination of need for ocean dumping.

    Science.gov (United States)

    2010-07-01

    ... ocean dumping. 227.16 Section 227.16 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Need for Ocean Dumping § 227.16 Basis for determination of need for ocean dumping. (a) A need for ocean...

  1. 48 CFR 227.7011 - Procurement of rights in inventions, patents, and copyrights.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Procurement of rights in inventions, patents, and copyrights. 227.7011 Section 227.7011 Federal Acquisition Regulations System DEFENSE... COPYRIGHTS Infringement Claims, Licenses, and Assignments 227.7011 Procurement of rights in inventions...

  2. 48 CFR 1852.227-71 - Requests for waiver of rights to inventions.

    Science.gov (United States)

    2010-10-01

    ... rights to inventions. 1852.227-71 Section 1852.227-71 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-71 Requests for waiver of rights to inventions. As prescribed in 1827.30-70(c... Technology: Requests for Waiver of Rights to Inventions (APR 1984) (a) In accordance with the NASA Patent...

  3. 48 CFR 52.227-2 - Notice and Assistance Regarding Patent and Copyright Infringement.

    Science.gov (United States)

    2010-10-01

    ... Regarding Patent and Copyright Infringement. 52.227-2 Section 52.227-2 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.227-2 Notice and Assistance Regarding Patent and Copyright... and Copyright Infringement (DEC 2007) (a) The Contractor shall report to the Contracting Officer...

  4. 48 CFR 227.7203-15 - Subcontractor rights in computer software or computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-15 Subcontractor rights in computer software or computer software documentation. (a... computer software or computer software documentation. 227.7203-15 Section 227.7203-15 Federal Acquisition...

  5. 48 CFR 227.7202-3 - Rights in commercial computer software or commercial computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7202-3 Rights in commercial computer software or commercial computer software documentation... computer software or commercial computer software documentation. 227.7202-3 Section 227.7202-3 Federal...

  6. 40 CFR 227.32 - Liquid, suspended particulate, and solid phases of a material.

    Science.gov (United States)

    2010-07-01

    ... MATERIALS Definitions § 227.32 Liquid, suspended particulate, and solid phases of a material. (a) For the... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Liquid, suspended particulate, and solid phases of a material. 227.32 Section 227.32 Protection of Environment ENVIRONMENTAL PROTECTION...

  7. 20 CFR 725.227 - Time of determination of relationship and dependency of survivors.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Time of determination of relationship and dependency of survivors. 725.227 Section 725.227 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION... Benefits) § 725.227 Time of determination of relationship and dependency of survivors. The determination as...

  8. 40 CFR 227.2 - Materials which satisfy the environmental impact criteria of subpart B.

    Science.gov (United States)

    2010-07-01

    ... environmental impact criteria of subpart B. 227.2 Section 227.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS General § 227.2 Materials which satisfy the environmental impact criteria of subpart...

  9. What Shaped Elias 2-27's Disk?

    Science.gov (United States)

    Kohler, Susanna

    2017-04-01

    The young star Elias 2-27 is surrounded by a massive disk with spectacular spiral arms. A team of scientists from University of Cambridges Institute of Astronomy has now examined what might cause this disks appearance.Top: ALMA 1.3-mm observations of Elias 2-27s spiral arms, processed with an unsharp masking filter. Two symmetric spiral arms, a bright inner ellipse, and two dark crescents are clearly visible. Bottom: a deprojection of the top image (i.e., what the system would look like face-on). [Meru et al. 2017]ALMA-Imaged Spiral ArmsWith the dawn of new telescopes such as the Atacama Large Millimeter/submillimeter Array, were now able to study the birth of young stars and their newly forming planetary systems in more detail than ever before. But these new images require new models and interpretations!Case in point: Elias 2-27 is a low-mass star thats only a million years old and is surrounded by an unusually massive disk of gas and dust. Recent spatially-resolved ALMA observations of Elias 2-27 have revealed the stunning structure of the stars disk: it contains two enormous, symmetric spiral arms, as well as additional features interior to the spirals.What caused the disk to develop this structure? Led by Farzana Meru, a group of Institute of Astronomy researchers has run a series of simulations that explore different ways that Elias 2-27s disk might have evolved into the shape we see today.Modeling a DiskMeru and collaborators performed a total of 72 three-dimensional smoothed particle hydrodynamics simulations tracking 250,000 gas particles in a model disk around a star like Elias 2-27. They then modeled the transfer of energy through these simulated disks and produced synthetic ALMA observations based on the outcomes.Left: Synthetic ALMA observations of disks shaped by an internal companion (top), an external companion (middle), and gravitational instability within the disk (bottom). Right: Deprojections of the images on the left. Scales are the same as in

  10. Development of ion beam sputtering techniques for actinide target preparation

    Science.gov (United States)

    Aaron, W. S.; Zevenbergen, L. A.; Adair, H. L.

    1985-06-01

    Ion beam sputtering is a routine method for the preparation of thin films used as targets because it allows the use of a minimum quantity of starting material, and losses are much lower than most other vacuum deposition techniques. Work is underway in the Isotope Research Materials Laboratory (IRML) at ORNL to develop the techniques that will make the preparation of actinide targets up to 100 μg/cm 2 by ion beam sputtering a routinely available service from IRML. The preparation of the actinide material in a form suitable for sputtering is a key to this technique, as is designing a sputtering system that allows the flexibility required for custom-ordered target production. At present, development work is being conducted on low-activity actinides in a bench-top system. The system will then be installed in a hood or glove box approved for radioactive materials handling where processing of radium, actinium, and plutonium isotopes among others will be performed.

  11. Putative regulation mechanism for the MSTN gene by a CpG island generated by the SINE marker Ins227bp.

    Science.gov (United States)

    van den Hoven, René; Gür, Emre; Schlamanig, Manuela; Hofer, Martin; Onmaz, Ali Cesur; Steinborn, Ralf

    2015-06-23

    A single nucleotide polymorphism (SNP) in the first intron of the myostatin gene (MSTN) is associated with aptness of elite Thoroughbreds to race over sprint, middle or long distances. This intronic marker (g.66493737 T ≻ C), a short interspersed nuclear element (SINE) of 227 bp (Ins227bp) insertion polymorphism in the MSTN promoter, and the adjacent SNP BIEC2-417495 have not been studied for their association with racing aptness of the average Thoroughbreds raced in countries with lower status of the racing industry. This study investigated these markers regarding their prevalence and association with performance in common race horses. Markers were genotyped by amplification refractory mutation system-quantitative PCR (ARMS-qPCR) or amplicon melting. Furthermore, we asked whether the Ins227bp marker might theoretically regulate the expression of myostatin by generating a novel target for DNA methylation or by changing binding sites for transcription factors. Putative sites for DNA methylation or binding of transcription factors were predicted by MethPrimer and by the softwares JASPAR, MatInspector and UniPROBE, respectively. Pairwise linkage disequilibrium between g.66493737 T ≻ C and Ins227bp was high (r (2) = 0.93). A lower linkage was determined for g.66493737 T ≻ C and BIEC2-417495 (r (2) = 0.69) as well as for BIEC2-417495 and Ins227bp (r (2) = 0.76). The estimated frequencies for the presence of Ins227bp (I) indel and the C alleles at g.66493737 T ≻ C and BIEC2-417495 were 0.46, 0.47 and 0.43, respectively. Heterozygotes represented the most abundant genotype at each locus. The best racing distance (BRD) was significantly different between the homozygotes of each SNP (p = 0.01 to 0.03). C allele homozygotes at BIEC2-417495 or g.66493737 T ≻ C, as well as Ins227bp homozygotes earned most money on a mean distance ranging from 1211 to 1230 m. Heterozygotes earned most money on races over 1690 to 1709 m. The BRD for the T/T carriers at both SNP loci

  12. 48 CFR 227.7206 - Contracts for architect-engineer services.

    Science.gov (United States)

    2010-10-01

    ... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7206 Contracts for architect-engineer...

  13. 48 CFR 227.7103-15 - Subcontractor rights in technical data.

    Science.gov (United States)

    2010-10-01

    ... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS... Computer Software Previously Delivered to the Government; and (4) 252.227-7037, Validation of Restrictive...

  14. 48 CFR 227.7204 - Contracts under the Small Business Innovative Research Program.

    Science.gov (United States)

    2010-10-01

    ... DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7204 Contracts...

  15. 48 CFR 227.7203-12 - Government right to establish conformity of markings.

    Science.gov (United States)

    2010-10-01

    ..., DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-12... identified in the clause at 252.227-7014, Rights in Noncommercial Computer Software and Noncommercial Computer Software Documentation. All other markings are nonconforming markings. An authorized marking that...

  16. 48 CFR 227.7203-17 - Overseas contracts with foreign sources.

    Science.gov (United States)

    2010-10-01

    ... COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-17 Overseas contracts with foreign sources. (a) The clause at 252.227-7032, Rights in Technical Data and Computer Software... Noncommercial Computer Software and Noncommercial Computer Software Documentation, when the Government requires...

  17. [sup 227]Ac: a suggested long-lived multiple-line gamma-ray calibration standard

    Energy Technology Data Exchange (ETDEWEB)

    Aarle, J. van; Esterlund, R.A.; Patzelt, P. (Philipps Univ., Marburg (Germany)); Westmeier, W. (Gesellschaft fuer Kernspektrometrie mbH, Ebsdorfergrund-Moelln (Germany))

    1994-04-01

    X-ray and gamma-ray lines following the decay of [sup 227]Ac in transient equilibrium with its daughters were assayed via high-purity germanium-crystal (HPGe) spectrometry of a chemically purified [sup 227]Ac gamma-ray source. Relative emission probabilities were determined for 120 lines (I[sub [gamma

  18. 48 CFR 2453.227-70 - Form HUD-770, Report of Inventions and Subcontracts.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Form HUD-770, Report of Inventions and Subcontracts. 2453.227-70 Section 2453.227-70 Federal Acquisition Regulations System... HUD-770, Report of Inventions and Subcontracts. As prescribed in 2427.305-2, form HUD-770 shall be...

  19. 48 CFR 952.227-84 - Notice of right to request patent waiver.

    Science.gov (United States)

    2010-10-01

    ... patent waiver. 952.227-84 Section 952.227-84 Federal Acquisition Regulations System DEPARTMENT OF ENERGY... Notice of right to request patent waiver. Include this provision in all appropriate solicitations in accordance with 48 CFR 927.409(t). Right To Request Patent Waiver (FEB 1998) Offerors have the right to...

  20. 48 CFR 952.227-11 - Patent rights-retention by the contractor (short form).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Patent rights-retention by the contractor (short form). 952.227-11 Section 952.227-11 Federal Acquisition Regulations System.... The Contractor will file patent applications in additional countries or international patent offices...

  1. 48 CFR 227.675-1 - International Traffic in Arms Regulations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false International Traffic in Arms Regulations. 227.675-1 Section 227.675-1 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND...

  2. 48 CFR 252.227-7039 - Patents-reporting of subject inventions.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Patents-reporting of... CLAUSES Text of Provisions And Clauses 252.227-7039 Patents—reporting of subject inventions. As prescribed in 227.303(1), use the following clause: Patents—Reporting of Subject Inventions (APR 1990) The...

  3. 48 CFR 252.227-7014 - Rights in noncommercial computer software and noncommercial computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... documentation. (d) Third party copyrighted computer software or computer software documentation. The Contractor... Government under any patent. (j) Limitation on charges for rights in computer software or computer software... computer software and noncommercial computer software documentation. 252.227-7014 Section 252.227-7014...

  4. 48 CFR 252.227-7012 - Patent license and release contract.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Patent license and release... of Provisions And Clauses 252.227-7012 Patent license and release contract. As prescribed at 227.7012, insert the following clause in patent releases, license agreements, and assignments: (Contract No...

  5. 37 CFR 2.27 - Pending trademark application index; access to applications.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Pending trademark application index; access to applications. 2.27 Section 2.27 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Application for...

  6. 25 CFR 227.18 - Free use of gas by lessor.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Free use of gas by lessor. 227.18 Section 227.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND... desired school or other buildings belonging to the tribe, by making his own connections to a regulator...

  7. 42 CFR 435.227 - Individuals under age 21 who are under State adoption assistance agreements.

    Science.gov (United States)

    2010-10-01

    ... determines that— (i) At the time of the adoption placement, the child had special needs for medical or rehabilitative care that made the child difficult to place; and (ii) There is in effect an adoption assistance... adoption assistance agreements. 435.227 Section 435.227 Public Health CENTERS FOR MEDICARE & MEDICAID...

  8. 7 CFR Appendix to Part 227 - Apportionment of Funds for Nutrition Education and Training

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Apportionment of Funds for Nutrition Education and... NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM Pt. 227, App. Appendix to Part 227—Apportionment of Funds for Nutrition Education and Training...

  9. 48 CFR 252.227-7007 - License term-running royalty.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false License term-running... of Provisions And Clauses 252.227-7007 License term—running royalty. As prescribed at 227.7009-4(b), insert the following clause in patent releases, license agreements, and assignments: License Term—Running...

  10. 48 CFR 227.7009-3 - Additional clauses-contracts except running royalty contracts.

    Science.gov (United States)

    2010-10-01

    ...-contracts except running royalty contracts. 227.7009-3 Section 227.7009-3 Federal Acquisition Regulations...—contracts except running royalty contracts. The following clauses are examples for use in patent release and settlement agreements, and license agreements not providing for payment by the Government of a running...

  11. 48 CFR 252.227-7006 - License grant-running royalty.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false License grant-running... of Provisions And Clauses 252.227-7006 License grant—running royalty. As prescribed at 227.7009-4(a...—Running Royalty (AUG 1984) (a) The Contractor hereby grants to the Government, as represented by the...

  12. 48 CFR 252.227-7016 - Rights in bid or proposal information.

    Science.gov (United States)

    2010-10-01

    ... with respect to technical data or computer software contained in the Contractor's bid or proposal that... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Rights in bid or proposal... of Provisions And Clauses 252.227-7016 Rights in bid or proposal information. As prescribed in 227...

  13. 48 CFR 227.7203-8 - Deferred delivery and deferred ordering of computer software and computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-8 Deferred delivery and deferred ordering of computer software and computer... deferred ordering of computer software and computer software documentation. 227.7203-8 Section 227.7203-8...

  14. 40 CFR 227.14 - Criteria for evaluating the need for ocean dumping and alternatives to ocean dumping.

    Science.gov (United States)

    2010-07-01

    ... ocean dumping and alternatives to ocean dumping. 227.14 Section 227.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Need for Ocean Dumping § 227.14 Criteria for evaluating the need for ocean...

  15. In vivo detection of prion amyloid plaques using [{sup 11}C]BF-227 PET

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, Nobuyuki; Yanai, Kazuhiko [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Shiga, Yusei; Itoyama, Yasuhito [Tohoku University School of Medicine, Department of Neurology, Sendai (Japan); Furumoto, Shozo [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Tashiro, Manabu [Tohoku University, Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Sendai (Japan); Tsuboi, Yoshio [Fukuoka University School of Medicine, Department of Neurology, Fukuoka (Japan); Furukawa, Katsutoshi; Arai, Hiroyuki [Institute of Development, Aging, and Cancer, Tohoku University, Department of Geriatrics and Gerontology, Division of Brain Sciences, Sendai (Japan); Iwata, Ren [Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Innovation of New Biomedical Engineering Center, Sendai (Japan); Doh-ura, Katsumi [Tohoku University School of Medicine, Department of Prion Research, 2-1 Seiryo-machi, Aoba-ku, Sendai (Japan)

    2010-05-15

    In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain. The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straeussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [{sup 11}C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention. Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain. Although [{sup 11}C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs. (orig.)

  16. J. Genet. classic 227 NOTE: The pagination in the original included ...

    Indian Academy of Sciences (India)

    Unknown

    , December 2005. 227. NOTE: The pagination in the original included the reverse of plate 1 on p. 445, which was a blank. The blank is not included here, but the original page numbers have been retained.

  17. Dicty_cDB: VSF227 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available L22219 |L22219.1 Plasmodium falciparum transmission-blocking target antigen (s230) gene, 5' end. 38 0.15 3...|AF269242.1 Plasmodium falciparum transmission-blocking target antigen Pfs230 (s230) gene, complete cds...L08135 |L08135.1 Plasmodium falciparum transmission blocking target antigen (Ps230) mRNA, complete cds. 38

  18. 48 CFR 227.7107-1 - Architectural designs and data clauses for architect-engineer or construction contracts.

    Science.gov (United States)

    2010-10-01

    ... data clauses for architect-engineer or construction contracts. 227.7107-1 Section 227.7107-1 Federal... designs and data clauses for architect-engineer or construction contracts. (a) Except as provided in... (Unlimited), in solicitations and contracts for architect-engineer services and for construction involving...

  19. 40 CFR 227.3 - Materials which do not satisfy the environmental impact criteria set forth in subpart B.

    Science.gov (United States)

    2010-07-01

    ... environmental impact criteria set forth in subpart B. 227.3 Section 227.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR... environmental impact criteria of subpart B of this part, the Administrator or the Regional Administrator, as the...

  20. 48 CFR 227.7009-4 - Additional clauses-contracts providing for payment of a running royalty.

    Science.gov (United States)

    2010-10-01

    ...-contracts providing for payment of a running royalty. 227.7009-4 Section 227.7009-4 Federal Acquisition... clauses—contracts providing for payment of a running royalty. The clauses set forth below are examples... desired to cover the subject matter thereof and the contract provides for payment of a running royalty. (a...

  1. 48 CFR 227.7104 - Contracts under the Small Business Innovation Research (SBIR) Program.

    Science.gov (United States)

    2010-10-01

    ... PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7104 Contracts under the Small Business... Data and Computer Software—Small Business Innovation Research (SBIR) Program, when technical data or computer software will be generated during performance of contracts under the SBIR program. (b) Under the...

  2. 48 CFR 227.7103-8 - Deferred delivery and deferred ordering of technical data.

    Science.gov (United States)

    2010-10-01

    ..., DATA, AND COPYRIGHTS Rights in Technical Data 227.7103-8 Deferred delivery and deferred ordering of... or Computer Software, when it is in the Government's interests to defer the delivery of technical... items (other than technical data or computer software) under the contract or contract termination...

  3. 48 CFR 227.7203-13 - Government right to review, verify, challenge and validate asserted restrictions.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227..., reproduce, release, or disclose computer software or computer software documentation do not, by themselves, determine the extent of the Government's rights in such software or documentation. The Government may...

  4. 30 CFR 250.227 - What environmental impact analysis (EIA) information must accompany the EP?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What environmental impact analysis (EIA... and Information Contents of Exploration Plans (ep) § 250.227 What environmental impact analysis (EIA... requirements. Your EIA must: (1) Assess the potential environmental impacts of your proposed exploration...

  5. 48 CFR 1852.227-85 - Invention reporting and rights-Foreign.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Invention reporting and... Provisions and Clauses 1852.227-85 Invention reporting and rights—Foreign. As prescribed in 1827.303-70(f), insert the following clause: Invention Reporting and Rights—Foreign (APR 1986) (a) As used in this clause...

  6. 48 CFR 3053.227-70 - Conveyance of invention rights acquired by the Government.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Conveyance of invention... Prescription of Forms 3053.227-70 Conveyance of invention rights acquired by the Government. The following form is prescribed for including a means for contractors to report inventions made in the course of...

  7. 48 CFR 52.227-10 - Filing of Patent Applications-Classified Subject Matter.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Filing of Patent... Text of Provisions and Clauses 52.227-10 Filing of Patent Applications—Classified Subject Matter. As prescribed at 27.203-2, insert the following clause: Filing of Patent Applications—Classified Subject Matter...

  8. 48 CFR 227.7009 - Patent releases, license agreements, and assignments.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Patent releases, license... ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Infringement Claims, Licenses, and Assignments 227.7009 Patent releases, license agreements, and...

  9. 30 CFR 227.102 - What royalty management functions will MMS not delegate?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What royalty management functions will MMS not... MINERALS REVENUE MANAGEMENT DELEGATION TO STATES Delegation of Mms Royalty Functions § 227.102 What royalty management functions will MMS not delegate? This section lists the principal royalty management functions...

  10. 30 CFR 227.101 - What royalty management functions may MMS delegate to a State?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What royalty management functions may MMS... THE INTERIOR MINERALS REVENUE MANAGEMENT DELEGATION TO STATES Delegation of Mms Royalty Functions § 227.101 What royalty management functions may MMS delegate to a State? (a) If there are oil and gas...

  11. 77 FR 22835 - Second Meeting: RTCA Special Committee 227, Standards of Navigation Performance

    Science.gov (United States)

    2012-04-17

    ... minutes Review of NextGen PBN Integrated Portfolio and Strategy Activities Review/Discussion/Approval of... Plenary discussion/update of updates/changes Review of What's Applicable to MOPS Other Business Establish... 7-11, 2012 Welcome/Introductions/Administrative Remarks Agenda Overview Review of SC-227 Workspace...

  12. 48 CFR 52.227-7 - Patents-Notice of Government Licensee.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Patents-Notice of... Clauses 52.227-7 Patents—Notice of Government Licensee. As prescribed at 27.202-5(b), insert the following provision: Patents—Notice of Government Licensee (APR 1984) The Government is obligated to pay a royalty...

  13. 5 CFR 591.227 - What adjustment factors does OPM add to the price indexes?

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false What adjustment factors does OPM add to...-Nonforeign Areas Cost-Of-Living Allowances § 591.227 What adjustment factors does OPM add to the price indexes? OPM adds to the price index an adjustment factor that reflects differences in need, access to and...

  14. 48 CFR 52.227-4 - Patent Indemnity-Construction Contracts.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Patent Indemnity... Clauses 52.227-4 Patent Indemnity—Construction Contracts. As prescribed in 27.201-2(d)(1), insert the following clause: Patent Indemnity—Construction Contracts (DEC 2007) Except as otherwise provided, the...

  15. 25 CFR 227.25 - Inspection of premises, books and accounts.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Inspection of premises, books and accounts. 227.25... Inspection of premises, books and accounts. Lessee shall agree to allow the lessor and his agents or any... Department; and their books and records, showing manner of operations and persons interested, shall be open...

  16. 48 CFR 1852.227-72 - Designation of new technology representative and patent representative.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT CLAUSES Texts of Provisions and Clauses 1852.227-72 Designation of new technology representative... of New Technology Representative and Patent Representative (JUL 1997) (a) For purposes of administration of the clause of this contract entitled “New Technology” or “Patent Rights—Retention by the...

  17. The Political Discourse of the Campaign against Bilingual Education: From "Proposition 227" to "Horne v. Flores"

    Science.gov (United States)

    Yamagami, Mai

    2012-01-01

    Using the frameworks of critical discourse analysis, representation theory, and legitimization theory, this study examines the political discourse of the campaign for Proposition 227 in California--particularly, the key social representations of languages, their speakers, and the main political actors in the campaign. The analysis examines the…

  18. 7 CFR 227.37 - State plan for nutrition education and training.

    Science.gov (United States)

    2010-01-01

    ... advice and recommendations of the National Advisory Council on Child Nutrition, State educational or... 7 Agriculture 4 2010-01-01 2010-01-01 false State plan for nutrition education and training. 227... NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING...

  19. Outcomes From AAS Hack Day at the 227th AAS Meeting

    Science.gov (United States)

    Kohler, Susanna

    2016-01-01

    will be a huge first step.Gender in Astronomy Conferences: Jim Davenport (WWU), Ben Nelson (Northwestern), Mehmet Alpsalan (NASA Ames), and Erin Maier (University of Iowa) analyzed data collected during the conference on the gender breakdown of who asks questions after oral presentations. Now in its third year, one new finding from the study is that women dont ask questions as much as men do, but they tend to ask questions more when the speaker is a woman or the first question-asker is a woman.More from #hackaas at #aas227: Gender of speaker vs. 1st to ask a question for all 3 years of Gender in Astro survey pic.twitter.com/l74D3rSUOD Erin Maier (@fallelujah) January 9, 2016The Early Reference Project: Many pre-1950 publications lack up-to-date citation information because the text is digitally archived as an image. Brendan Wells (UC Santa Cruz) worked with representatives from ADS and Zooniverse to set up a crowd-sourced platform to identify references in these old papers.Glassdome: Ellie Schwab (CUNY) and colleagues Paige Godfrey, Munazza Alam, and Cam Buzzard began work on a website modeled after glassdoor for safely sharing experiences throughout their astronomy careers. Glassdome will feature career path stories, department reviews, and salaries, all optionally anonymous. The site is hosted by ScienceBetter and is under development.Observing Run Sharing: Sometimes near the end of a long night at the telescope you have observed everything you need but still have time left. Short of choosing randomly or hoping a colleague is online in the middle of the night, there is currently no good solution. To address this, Brooke Simmons (UC San Diego) designed a web app that would allow astronomers to submit their favorite night sky targets. The project is still a work in progress.ArXiv Podcast: Ruth Angus (Oxford) started a podcast featuring astronomers summarizing their new papers submitted to astro-ph in one minute. Its like audio astrobites! If youve recently published a

  20. Efforts to control the errant products of a targeted in vivo generator.

    Science.gov (United States)

    Jaggi, Jaspreet Singh; Kappel, Barry J; McDevitt, Michael R; Sgouros, George; Flombaum, Carlos D; Cabassa, Catalina; Scheinberg, David A

    2005-06-01

    Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides. The daughters, especially bismuth-213 (213Bi), tend to accumulate in the kidneys. We tested the efficacy of various pharmacologic agents and the effect of tumor burden in altering the pharmacokinetics of the 225Ac daughters to modify their renal uptake. Pharmacologic treatments in animals were started before i.v. administration of the HuM195-225Ac generator. 225Ac, francium-221 (221Fr), and 213Bi biodistributions were calculated in each animal at different time points after 225Ac generator injection. Oral metal chelation with 2,3-dimercapto-1-propanesulfonic acid (DMPS) or meso-2,3-dimercaptosuccinic acid (DMSA) caused a significant reduction (P < 0.0001) in the renal 213Bi uptake; however, DMPS was more effective than DMSA (P < 0.001). The results with DMPS were also confirmed in a monkey model. The renal 213Bi and 221Fr activities were significantly reduced by furosemide and chlorothiazide treatment (P < 0.0001). The effect on renal 213Bi activity was further enhanced by the combination of DMPS with either chlorothiazide or furosemide (P < 0.0001). Competitive antagonism by bismuth subnitrate moderately reduced the renal uptake of 213Bi. The presence of a higher target-tumor burden significantly prevented the renal 213Bi accumulation (P = 0.003), which was further reduced by DMPS treatment (P < 0.0001). Metal chelation, diuresis with furosemide or chlorothiazide, and competitive metal blockade may be used as adjuvant therapies to modify the renal accumulation of 225Ac daughters.

  1. Chloroform degradation in methanogenic methanol enrichment cultures and by Methanosarcina barkeri 227.

    OpenAIRE

    Bagley, D M; Gossett, J M

    1995-01-01

    The effects of methanol addition and consumption on chloroform degradation rate and product distribution in methanogenic methanol enrichment cultures and in cultures of Methanosarcina barkeri 227 were investigated. Degradation of chloroform with initial concentrations up to 27.3 microM in enrichment cultures and 4.8 microM in pure cultures was stimulated by the addition of methanol. However, methanol consumption was inhibited by as little as 2.5 microM chloroform in enrichment cultures and 0....

  2. Cultural Resources Mitigation Along Ditch 19, Site 23DU227, Dunklin County, Missouri

    Science.gov (United States)

    1984-06-01

    site from the late Archaic through Mississippian periods. There is a good possibility of pollen and phytolith interpretation. It is recommended that this...providing me with pollen and phytolith results within the time I needed them. Lillie Weeams proved to be a capable word processor and is sincerely thanked...138 APPENDIX D. Gross Counts of Artifact Categories by General Provenience at Site 23DU227 141 APPENDIX E. Pollen and Phytolith Analysis of Sediments

  3. Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium.

    Directory of Open Access Journals (Sweden)

    Roberta d'Emmanuele di Villa Bianca

    Full Text Available Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity.

  4. 48 CFR 227.7203-16 - Providing computer software or computer software documentation to foreign governments, foreign...

    Science.gov (United States)

    2010-10-01

    ... software or computer software documentation to foreign governments, foreign contractors, or international... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-16 Providing computer software...

  5. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  6. Interactions between nitrogen fixation and osmoregulation in the methanogenic archaeon Methanosarcina barkeri 227

    Energy Technology Data Exchange (ETDEWEB)

    Brabban, A.D.; Orcutt, E.N.; Zinder, S.H. [Cornell Univ., Ithaca, NY (United States). Section of Microbiology

    1999-03-01

    The nitrogenase enzyme complex of Methanosarcina barkeri 227 was found to be more sensitive to NaCl than previously studied molybdenum nitrogenases are, with total inhibition of activity occurring at 190 mM NaCl, compared with >600 mM NaCl for Azotobacter vinelandii and Clostridium pasteurianum nitrogenases. Na{sup +} and K{sup +} had equivalent effects, whereas Mg{sup 2+} was more inhibitory than either monovalent cation, even on a per-charge basis. The anion Cl{sup {minus}} was more inhibitory than acetate was. Because M. barkeri 227 is a facultative halophile, the authors examined the effects of external salt on growth and diazotrophy and found that inhibition of growth was not greater with N{sub 2} than with NH{sub 4}{sup +}. Cells grown with N{sub 2} and cells grown with NH{sub 4}{sup +} produced equal concentrations of {alpha}-glutamate at low salt concentrations and equal concentrations of N{sup {var_epsilon}}-acetyl-{beta}-lysine at NaCl concentrations greater than 500 mM. Despite the high energetic cost of fixing nitrogen for these osmolytes, the authors obtained no evidence that there is a shift towards nonnitrogenous osmolytes during diazotrophic growth. In vitro nitrogenase enzyme assays showed that at a low concentration potassium glutamate enhanced activity but at higher concentrations this compound inhibited activity; 50% inhibition occurred at a potassium glutamate concentration of approximately 400 mM.

  7. Variations in meteor heights at 22.7° S during solar cycle 23

    Science.gov (United States)

    Lima, Lourivaldo; Takahashi, Hisao; Clemesha, Barclay; Batista, Paulo; Rodrigues de Araujo, Luciana; Alves, Edvaldo de O.

    Meteoroids impinging on Earth’s upper atmosphere ablate and form meteor ionized trails, which are able to reflect and scatter incident radio waves in the high frequency (HF) and very high frequency (VHF) bands. From radar measurements it is possible to determinate meteor trails and atmospheric characteristics in the MLT region. In this work, measurements obtained at Cachoeira Paulista (22.7° S, 45.0° W) by SKiYMET radar system, has been used to investigate long-term trends in the peak altitude of the meteor layer during solar cycle 23. The peak heights were analyzed with respect to a possible long-term trend and solar activity-induced variations by linear fitting and the results have revealed a linear decadal decrease of about 1.1 km for meteor peak heights. In this paper will discuss the possible solar effect in the meteor peak height variations.

  8. A compiled catalogue of reference stars around 227 ICRF extragalactic radio sources.

    Science.gov (United States)

    Ryl'kov, V. P.; Narizhnaya, N. V.; Dement'eva, A. A.; Pinigin, G. I.; Maigurova, N. V.; Martinov, M. V.

    A compiled catalogue of21440 stars with magnitudes from 10 to 17 is prepared on the basis of original observations made from the end of the 20th to the beginning of the 21th century. The catalogue con tains 227 fields of the cetes tial sphere around extragalactic radio sources in a declination zone from -17 to +89°. The field size is 40' for both right ascension and declination. The internal accuracy of positions for both coordinates is not worse than 0.1". The comparison of stellar positions with the use of the UCAC2 and CMC13 catalogues shows that the average external accuracy is about 0.05-0.15" for the majority ofchosenfields of the compiled catalogue. The positions of 10795 stars up to +50° in declination are given at epoch J2000.0, whereas the positions of other stars are given at the epoch of an observation.

  9. Statistical analysis and optimization of direct metal laser deposition of 227-F Colmonoy nickel alloy

    Science.gov (United States)

    Angelastro, A.; Campanelli, S. L.; Casalino, G.

    2017-09-01

    This paper presents a study on process parameters and building strategy for the deposition of Colmonoy 227-F powder by CO2 laser with a focal spot diameter of 0.3 mm. Colmonoy 227-F is a nickel alloy especially designed for mold manufacturing. The substrate material is a 10 mm thick plate of AISI 304 steel. A commercial CO2 laser welding machine was equipped with a low-cost powder feeding system. In this work, following another one in which laser power, scanning speed and powder flow rate had been studied, the effects of two important process parameters, i.e. hatch spacing and step height, on the properties of the built parts were analysed. The explored ranges of hatch spacing and step height were respectively 150-300 μm and 100-200 μm, whose dimensions were comparable with that of the laser spot. The roughness, adhesion, microstructure, microhardness and density of the manufactured specimens were studied for multi-layer samples, which were made of 30 layers. The statistical significance of the studied process parameters was assessed by the analysis of the variance. The process parameters used allowed to obtain both first layer-to-substrate and layer-to-layer good adhesions. The microstructure was fine and almost defect-free. The microhardness of the deposited material was about 100 HV higher than that of the starting powder. The density as high as 98% of that of the same bulk alloy was more than satisfactory. Finally, simultaneous optimization of density and roughness was performed using the contour plots.

  10. Accelerating growth of HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane) in the atmosphere

    DEFF Research Database (Denmark)

    Laube, J.C.; Martinerie, P.; Witrant, E.

    2010-01-01

    We report the first measurements of 1,1,1,2,3,3,3-heptafluoropropane (HFC-227ea), a substitute for ozone depleting compounds, in air samples originating from remote regions of the atmosphere and present evidence for its accelerating growth. Observed mixing ratios ranged from below 0.01 ppt in dee...

  11. 48 CFR 227.7203-10 - Contractor identification and marking of computer software or computer software documentation to...

    Science.gov (United States)

    2010-10-01

    ... and marking of computer software or computer software documentation to be furnished with restrictive... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-10 Contractor identification and...

  12. Beliefs about Bilingualism, Bilingual Education, and Dual Language Development of Early Childhood Preservice Teachers Raised in a Prop 227 Environment

    Science.gov (United States)

    Garrity, Sarah; Aquino-Sterling, Cristian R.; Van Liew, Charles; Day, Ashley

    2018-01-01

    Despite the well-documented benefits of bilingualism, current educational practices in the United States reflect the deeply held belief that because the United States is an English speaking country, English should be the language of instruction. This belief was codified into law in California via the 1998 passage of Proposition 227, which banned…

  13. Latino Parents' "Choice" for Bilingual Education in an Urban California School: Language Politics in the Aftermath of Proposition 227

    Science.gov (United States)

    Monzo, Lilia D.

    2005-01-01

    This paper examines the choices parents have made regarding language of instruction in their children's classrooms, particularly in California after the implementation of Proposition 227. The data for this study are drawn from a 2-year ethnography of eight Latino families from an urban immigrant Latino community. The parents in the study held a…

  14. 48 CFR 252.227-7018 - Rights in noncommercial technical data and computer software-Small Business Innovation Research...

    Science.gov (United States)

    2010-10-01

    ... technical data and computer software-Small Business Innovation Research (SBIR) Program. 252.227-7018 Section... Noncommercial Technical Data and Computer Software—Small Business Innovation Research (SBIR) Program (JUN 1995... the Rights in Noncommercial Technical Data and Computer Software—Small Business Innovative Research...

  15. 27 CFR 28.227 - Removals of beer by persons other than the brewer or agent of the brewer.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Removals of beer by... ALCOHOL Exportation of Beer With Benefit of Drawback Execution of Claims § 28.227 Removals of beer by persons other than the brewer or agent of the brewer. Where there is a removal of taxpaid beer by a person...

  16. 48 CFR 227.7203-3 - Early identification of computer software or computer software documentation to be furnished to...

    Science.gov (United States)

    2010-10-01

    ..., DATA, AND COPYRIGHTS Rights in Computer Software and Computer Software Documentation 227.7203-3 Early identification of computer software or computer software documentation to be furnished to the Government with... computer software or computer software documentation to be furnished to the Government with restrictions on...

  17. EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype-phenotype correlation?

    NARCIS (Netherlands)

    Maclean, K.; Holme, S.A.; Gilmour, E.; Taylor, M.; Scheffer, H.; Graf, N.; Smith, G.H.; Onikul, E.; Bokhoven, J.H.L.M. van; Moss, C.; Ades, L.C.

    2007-01-01

    We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary syndrome (LMS). Features common to both families were an

  18. 48 CFR 227.7203-14 - Conformity, acceptance, and warranty of computer software and computer software documentation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Conformity, acceptance... Software Documentation 227.7203-14 Conformity, acceptance, and warranty of computer software and computer...) Conformity and acceptance. Solicitations and contracts requiring the delivery of computer software shall...

  19. 27 CFR 70.227 - Suspension of running of period of limitation; wrongful seizure of property of third party.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Suspension of running of... Limitations § 70.227 Suspension of running of period of limitation; wrongful seizure of property of third party. The running of the period of limitations on collection after assessment prescribed in 26 U.S.C...

  20. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  1. A Modified Adenovirus Vector–Mediated Antibody Screening Method Identifies EphA2 as a Cancer Target

    Directory of Open Access Journals (Sweden)

    Toshihiro Tanaka

    2017-08-01

    Full Text Available BACKGROUND: We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33. Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. METHODS: Hybridoma libraries producing monoclonal antibodies (mAbs were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33. Target antigens of the mAbs were identified by immunoprecipitation and mass spectrometry. Of these mAbs, we noted a clone, F2-27, that recognized the receptor tyrosine kinase EphA2. Next, we generated an adenovirus vector, Ax3CMTK-FZ33, that expressed a herpes simplex virus thymidine kinase (HSV-TK. The therapeutic efficacy of F2-27–mediated HSV-TK gene transduction, followed by ganciclovir (GCV administration, was studied in vitro. The inhibitory effect of F2-27 on cancer cell invasion was investigated by a three-dimensional spheroid formation assay. RESULTS: In vitro reporter gene expression after Adv-FZ33 infection via F2-27 was 146 times higher than with control mAb in EphA2-expressing cancer cell lines. F2-27–mediated Ax3CMTK-FZ33 infection induced the HSV-TK gene in an F2-27–dependent manner and had a highly effective cytotoxic effect in a GCV-dependent manner. Additionally, F2-27 independently inhibited migration of EphA2-positive breast cancer cell lines in three-dimensional culture. CONCLUSION: Our modified adenovirus and hybridoma screening system is useful for the development of targeted cancer therapy, and F2-27 has the potential to be an antibody-based therapy for various EphA2-positive cancers.

  2. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  3. Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis.

    Science.gov (United States)

    de Luca, Katie; Parkinson, Lynne; Downie, Aron; Blyth, Fiona; Byles, Julie

    2017-03-01

    The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio-demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis.

  4. Combined renin inhibition/(prorenin receptor blockade in diabetic retinopathy--a study in transgenic (mREN227 rats.

    Directory of Open Access Journals (Sweden)

    Wendy W Batenburg

    Full Text Available Dysfunction of renin-angiotensin system (RAS contributes to the pathogenesis of diabetic retinopathy (DR. Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (prorenin receptor ((PRR. Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (PRR blocker handle-region peptide (HRP on diabetic retinopathy in streptozotocin (STZ-induced diabetic transgenic (mRen227 rats (a model with high plasma prorenin levels as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen227 rats were randomly divided into the following groups: (1 non-diabetic; (2 diabetic treated with vehicle; (3 diabetic treated with aliskiren (10 mg/kg per day; and (4 diabetic treated with aliskiren+HRP (1 mg/kg per day. Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen227 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen227 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1α and TNF-α, and this was completely blocked by aliskiren or HRP, their combination, (PRR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (PRR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular

  5. Development of separation technology for the removal of radium-223 from targeted thorium conjugate formulations. Part II: purification of targeted thorium conjugates on cation exchange columns.

    Science.gov (United States)

    Frenvik, Janne Olsen; Dyrstad, Knut; Kristensen, Solveig; Ryan, Olav B

    2017-09-01

    Tumor targeting pharmaceuticals will play a crucial role in future pharma pipelines. The targeted thorium conjugate (TTC) therapeutic platform could provide real benefit to patients, whereby targeting moieties like monoclonal antibodies are radiolabelled with the alpha-emitting radionuclide thorium-227 ((227)Th, t1/2 = 18.7 days). A potential problem could be the accumulation of the long-lived daughter nuclide radium-223 ((223)Ra, t1/2 = 11.4 days) in the drug product during manufacturing and distribution. Therefore, the level of (223)Ra must be standardized before administration to the patient. The focus in this study has been the removal of (223)Ra, as the other progenies will have a very limited stay in the formulation. In this study, the purification of TTCs labeled with decayed (227)Th has been explored. Columns packed with a strong cation exchange resin have been used to sequester (223)Ra. The separation of TTC from (223)Ra has been evaluated as influenced by both formulation and process parameters with a design of experiments (DOE) study; including citrate or acetate buffer, pH, buffer concentration, presence or absence of pABA + EDTA, resin amount and sodium chloride concentration. The aim was to achieve a separation with high sorption of (223)Ra and accompanying low TTC sorption. The results were analyzed by multivariate analysis. Four regression models of TTC and (223)Ra sorption from citrate and acetate buffered formulations were developed. The predictive accuracy of sorption in the four statistical models was given by standard deviations and confidence intervals. The TTC sorption in citrate and acetate buffered formulations was affected by the identical variables and the variation in TTC sorption was comparable for the two models. However, the DOE variables had a significantly stronger impact on the (223)Ra sorption in citrate buffered formulations than the (223)Ra sorption in acetate buffer. An optimal separation with a TTC sorption

  6. Binding sites for. alpha. -bungarotoxin and the noncompetitive inhibitor phencyclidine on a synthetic peptide comprising residues 172-227 of the. alpha. -subunit of the nicotinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly-Roberts, D.L.; Lentz, T.L. (Yale Univ., New Haven, CT (United States))

    1991-07-30

    The binding of the competitive antagonist {alpha}-bungarotoxin ({alpha}-Btx) and the noncompetitive inhibitor phencyclidine (PCP) to a synthetic peptide comprising residues 172-227 of the {alpha}-subunit of the Torpedo acetylcholine receptor has been characterized. {sup 125}I-{alpha}-Btx bound to the 172-227 peptide in a solid-phase assay and was competed by {alpha}-Btx d-tubocurarine and NaCl. In the presence of 0.02% sodium dodecyl sulfate, {sup 125}I-{alpha}-Btx bound to the 56-residue peptide with a K{sub D} of 3.5 nM, as determined by equilibrium saturation binding studies. Because {alpha}Btx binds to a peptide comprising residues 173-204 with the same affinity and does not bind to a peptide comprising residues 205-227, the competitive antagonist and hence agonist binding site lies between residues 173 and 204. After photoaffinity labeling, ({sup 3}H)PCP was bound to the 172-227 peptide. ({sup 3}H)PCP binding was inhibited by chlorpromazine, tetracaine, and dibucaine. It is concluded that a high-affinity binding site for PCP is located between residues 205 and 227, which includes the first 18 residues of transmembrane segment M1, and that a low-affinity site is located in the competitive antagonist binding site between residues 173 and 204. These results show that a synthetic peptide comprising residues 172-227 of the {alpha} subunit contains three binding sites, one for {alpha}-Btx and two for PCP. Previous studies on the intact receptor indicate high-affinity PCP binding occurs in the receptor channel.

  7. Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate {sup 227}Th-rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein; Heyerdahl, Helen; Hjelmerud, Anne Kristine; Larsen, Roy H. [Oslo University Hospital, Department of Radiation Biology, The Norwegian Radium Hospital, Oslo (Norway); Jonasdottir, Thora J. [Norwegian School of Veterinary Science, Small Animal Section, Department of Companion Animal Clinical Sciences, Oslo (Norway); Nesland, Jahn M. [Oslo University Hospital, Division of Pathology, The Norwegian Radium Hospital, Oslo (Norway); University of Oslo, Faculty Division The Norwegian Radium Hospital, Medical Faculty, Oslo (Norway); Borrebaek, Joergen [Algeta AS, Oslo (Norway)

    2010-01-15

    The anti-CD20 antibody rituximab labelled with the {alpha}-particle-emitting radionuclide {sup 227}Th is of interest as a radiotherapeutic agent for treatment of lymphoma. Complete regression of human lymphoma Raji xenografts in 60% of mice treated with 200 kBq/kg {sup 227}Th-rituximab has been observed. To evaluate possible late side effects of {sup 227}Th-rituximab, the long-term radiotoxicity of this potential radiopharmaceutical was investigated. BALB/c mice were injected with saline, cold rituximab or 50, 200 or 1,000 kBq/kg {sup 227}Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji xenografts treated with various doses of {sup 227}Th-rituximab were also included in the study. Toxicity was evaluated by measurements of mouse body weight, white blood cell (WBC) and platelet counts, serum clinical chemistry parameters and histological examination of tissues. Only the 1,000 kBq/kg dosage resulted in decreased body weight of the BALB/c mice. There was a significant but temporary decrease in WBC and platelet count in mice treated with 400 and 1,000 kBq/kg {sup 227}Th-rituximab. Therefore, the no-observed-adverse-effect level (NOAEL) was 200 kBq/kg. The maximum tolerated activity was between 600 and 1,000 kBq/kg. No significant signs of toxicity were observed in histological sections in any examined tissue. There were significantly (p < 0.05), but transiently, higher concentrations of serum bile acids and aspartate aminotransferase in mice treated with either {sup 227}Th-rituximab or non-labelled antibody when compared with control mice. The maximum tolerated dose to bone marrow was between 2.1 and 3.5 Gy. Therapeutically relevant dose levels of {sup 227}Th-rituximab were well tolerated in mice. Bone marrow suppression, as indicated by decrease in WBC count, was the dose-limiting radiotoxicity. These toxicity data together with anti-tumour activity data in a CD20-positive xenograft mouse model indicate that therapeutic effects could be

  8. MEET ISOLDE - Target Production

    CERN Multimedia

    2017-01-01

    MEET ISOLDE - Target Production. Everything at ISOLDE starts with a target and the target production team realise on more then 50 years of experience to build and develop new targets for ISOLDE’s wide physics program.

  9. A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR)

    NARCIS (Netherlands)

    Kelly, DJ; Wilkinson-Berka, JL; Allen, TJ; Cooper, ME; Skinner, SL

    Background. The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. Methods. Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate

  10. Effects of aliskiren on blood pressure, albuminuria, and (Pro)renin receptor expression in diabetic TG(mRen-2)27 Rats

    NARCIS (Netherlands)

    D.L. Feldman (David); L. Jin (Li); H. Xuan (Hong); A. Contrepas (Aurelie); Y. Zhou (Yinong); R.L. Webb (Randy); D.N. Mueller (Dominik); S. Feldt (Sandra); F. Cumin (Frederick); W. Maniara (Wieslawa); E. Persohn (Elke); H. Schuetz (Helmut); A.H.J. Danser (Jan); G. Nguyen (Genevieve)

    2008-01-01

    textabstractThe aim of this study was to explore the effects of the renin inhibitor aliskiren in streptozotocin-diabetic TG(mRen-2)27 rats. Furthermore, we investigated in vitro the effect of aliskiren on the interactions between renin and the (pro)renin receptor and between aliskiren and prorenin.

  11. Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no [Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo (Norway); Røe, Kathrine [Department of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog (Norway); Brevik, Ellen Mengshoel [Department of Research and Development, Algeta ASA, Oslo (Norway); Dahle, Jostein [Nordic Nanovector AS, Oslo (Norway)

    2013-09-01

    Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.

  12. Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.

    Science.gov (United States)

    Kangussu, Lucas M; Guimaraes, Priscila S; Nadu, Ana Paula; Melo, Marcos B; Santos, Robson A S; Campagnole-Santos, Maria Jose

    2015-10-01

    Activation of the peripheral angiotensin-(1-7)/Mas axis of the renin-angiotensin system produces important cardioprotective actions, counterbalancing the deleterious actions of an overactivity of Ang II/AT1 axis. In the present study we evaluated whether the chronic increase in Ang-(1-7) levels in the brain could ameliorate cardiac disorders observed in transgenic (mRen2)27 hypertensive rats through actions on Mas receptor. Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats, instrumented with telemetry probe for arterial pressure (AP) measurement were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or Ang-(1-7) associated with Mas receptor antagonist (A779, 1 μg/h) or 0.9% sterile saline (0.5 μl/h) through osmotic mini-pumps. Ang-(1-7) infusion in (mRen2)27 rats reduced blood pressure, normalized the baroreflex control of HR, restored cardiac autonomic balance, reduced cardiac hypertrophy and pre-fibrotic alterations and decreased the altered imbalance of Ang II/Ang-(1-7) in the heart. In addition, there was an attenuation of the increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-β in the heart of (mRen2)27 rats. Furthermore, most of these effects were mediated in the brain by Mas receptor, since were blocked by its selective antagonist, A779. These data indicate that increasing Ang-(1-7) levels in the brain can attenuate cardiovascular disorders observed in (mRen2)27 hypertensive rats, probably by improving the autonomic balance to the heart due to centrally-mediated actions on Mas receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Categorization of sodium sieving by 2.27% and 3.86% peritoneal equilibration tests--a comparative analysis in the clinical setting.

    Science.gov (United States)

    Gomes, Ana Marta; Fontán, Miguel Pérez; Rodríguez-Carmona, Ana; Sastre, Arancha; Cambre, Helena Díaz; Muñiz, Andrés López; Falcón, Teresa García

    2009-11-01

    Analysis of the dialysate sodium concentration during a peritoneal equilibration test (PET) provides information on the rates of water and solute transport through different membrane pathways. A hypertonic (3.86%) glucose-based dialysate may enhance the accuracy of analysis. There are still gaps in our knowledge regarding this question, in the clinical setting. Objective. The aim of this study was to compare the categorization of the sodium sieving effect in peritoneal dialysis (PD) patients by 2.27% and 3.86% PETs, and to disclose clinical correlates of this phenomenon. Method. Ninety PD patients underwent prospectively 2.27% and 3.86% modified (dialysate samples at 0, 60, 90, 120 and 240 min) PETs, in a random order. We searched for differences in the time profiles of sodium sieving and its categorization. We correlated sodium sieving with ultrafiltration (UF) and solute transport capacity, as also with selected clinical and demographic variables, using a multivariate approach. The maximum dip in the dialysate sodium concentration (11.1 mM/L, 3.86% versus 7.1 mM/L, 2.27%, P sieving (defined by a dip sieving in the 2.27% test (100.0% sensitivity and 72.0% specificity, using 3.86% as a reference). UF and D/P(240 min) creatinine were independent predictors of the sodium sieving effect in both tests. Moreover, multivariate analysis disclosed a consistent inverse correlation between GFR and sodium sieving in both the 2.27% (B = -0.23, 95% CI -0.40, -0.07, P = 0.006) and 3.86% PET (B = -0.46, 95% CI -0.65, -0.26, P sieving in PD patients. However, the information provided by this test lacks the discriminatory capacity of the 3.86% PET, which should be considered the one for reference for this purpose. GFR keeps a consistent inverse correlation with the intensity of sodium sieving in both the 2.27% and 3.86% PET.

  14. The prevalence of ABCB1:c.227_230delATAG mutation in affected dog breeds from European countries.

    Science.gov (United States)

    Firdova, Zuzana; Turnova, Evelina; Bielikova, Marcela; Turna, Jan; Dudas, Andrej

    2016-06-01

    Deletion of 4-base pairs in the canine ABCB1 (MDR1) gene, responsible for encoding P-glycoprotein, leads to nonsense frame-shift mutation, which causes hypersensitivity to macrocyclic lactones drugs (e.g. ivermectin). To date, at least 12 purebred dog breeds have been found to be affected by this mutation. The aim of this study was to update information about the prevalence of ABCB1 mutation (c.227_230delATAG) in predisposed breeds in multiple European countries. This large scale survey also includes countries which were not involved in previous studies. The samples were collected in the period from 2012 to 2014. The overview is based on genotyping data of 4729 individuals. The observed mutant allele frequencies were 58.5% (Smooth Collie), 48.3% (Rough Collie), 35% (Australian Shepherd), 30.3% (Shetland Sheepdog), 28.1% (Silken Windhound), 26.1% (Miniature Australian Shepherd), 24.3% (Longhaired Whippet), 16.2% (White Swiss Shepherd) and 0% (Border Collie). The possible presence of an ABCB1 mutant allele in Akita-Inu breed has been investigated with negative results. This information could be helpful for breeders in optimization of their breeding strategy and for veterinarians when prescribing drug therapy for dogs of predisposed breeds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Analysis of the 227 bp short interspersed nuclear element (SINE) insertion of the promoter of the myostatin (MSTN) gene in different horse breeds

    OpenAIRE

    Stefania Dall'Olio; Emilio Scotti; Luca Fontanesi; Marco Tassinari

    2014-01-01

    The myostatin (MSTN) gene encodes a protein known to be a negative regulator of muscle mass in mammalian species. Different polymorphisms of the horse (Equus caballus) MSTN gene have been identified, including single nucleotide polymorphisms and a short interspersed nuclear element (SINE) insertion of 227 bp within the promoter of the gene. The SINE insertion has been associated with performance traits in Thoroughbred racehorses and it was proposed as a predictor of optimum racing distance. T...

  16. Targeted therapies for cancer

    Science.gov (United States)

    ... so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few different ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  17. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590...

  18. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590 spectrophotometer

  19. Study of the origin of elements of the uranium-235 family observed in excess in the vicinity of the experimental nuclear EL4 reactor under dismantling. Lessons got at this day and conclusions; Etude de l'origine des elements de la famille de l'uranium-235 observes en exces dans les environs du reacteur nucleaire experimental EL4 en cours de demantelement. Enseignements retires a ce jour et conclusion

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    This study resumes the discovery of an excess of actinium 227 found around by EL4 nuclear reactor actually in dismantling. The search for the origin of this excess revealed a real inquiry of investigation during three years. Because a nuclear reactor existed in this area a particular attention will have concerned this region. The doubt became the line of conduct to find the answer to the human or natural origin of this excess. Finally and against any evidence, it appears that the origin of this phenomenon was natural, consequence of the particular local geology. The detail of the different investigations is given: search of a possible correlation with the composition of elevations constituent of lanes, search (and underlining) of new sites in the surroundings of the Rusquec pond and the Plouenez station, study of the atmospheric deposits under winds of the nuclear power plant and in the east direction, search of a possible relationship with the gaseous effluents of the nuclear power plant in the past, historical study of radioactive effluents releases in the fifty last years by the analysis of the sedimentary deposits in the Saint-Herbiot reservoir, search of a possible correlation between the excess of actinium 227 and the nuclear power plant activity; search of a possible correlation with a human activity without any relationship with the nuclear activities, search of a correlation with the underground waters, search of a correlation with the geological context, collect of information on the possible transfers in direction of the food chain, determination of the radiological composition of the underground waters ( not perturbed by human activity), search of the cause of an excess of actinium 227 in the old channel of liquid effluents release of the nuclear power plant. The results are given and discussed. And contrary to all expectations the origin of the excess of actinium 227 is completely natural. (N.C.)

  20. Targets for Precision Measurements

    Science.gov (United States)

    Loveland, W.; Yao, L.; Asner, D. M.; Baker, R. G.; Bundgaard, J.; Burgett, E.; Cunningham, M.; Deaven, J.; Duke, D. L.; Greife, U.; Grimes, S.; Heffner, M.; Hill, T.; Isenhower, D.; Klay, J. L.; Kleinrath, V.; Kornilov, N.; Laptev, A. B.; Massey, T. N.; Meharchand, R.; Qu, H.; Ruz, J.; Sangiorgio, S.; Selhan, B.; Snyder, L.; Stave, S.; Tatishvili, G.; Thornton, R. T.; Tovesson, F.; Towell, D.; Towell, R. S.; Watson, S.; Wendt, B.; Wood, L.

    2014-05-01

    The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

  1. Setting Asset Performance Targets

    NARCIS (Netherlands)

    Green, D.; Hodkiewicz, M.; Masschelein, S.; Schoenmaker, R.; Muruvan, S.

    2015-01-01

    Setting targets is a common way for organisations to establish performance expectations. However the validity of targets is challenged when performance is influenced by factors beyond the control of the manager. This project examines the issue of target setting for a single asset performance measure

  2. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  3. Absolute rate constant and O(3P yield for the O(1D+N2O reaction in the temperature range 227 K to 719 K

    Directory of Open Access Journals (Sweden)

    S. A. Carl

    2008-10-01

    Full Text Available The absolute rate constant for the reaction that is the major source of stratospheric NOx, O(1D+N2O → products, has been determined in the temperature range 227 K to 719 K, and, in the temperature range 248 K to 600 K, the fraction of the reaction that yields O(3P. Both the rate constants and product yields were determined using a recently-developed chemiluminescence technique for monitoring O(1D that allows for higher precision determinations for both rate constants, and, particularly, O(3P yields, than do other methods. We found the rate constant, kR1, to be essentially independent of temperature between 400 K and 227 K, having a value of (1.37±0.11×10−10 cm3 s−1, and for temperatures greater than 450 K a marked decrease in rate constant was observed, with a rate constant of only (0.94±0.11×10−10 cm3 s−1 at 719 K. The rate constants determined over the 227 K–400 K range show very low scatter and are significantly greater, by 20% at room temperature and 15% at 227 K, than the current recommended values. The fraction of O(3P produced in this reaction was determined to be 0.002±0.002 at 250 K rising steadily to 0.010±0.004 at 600 K, thus the channel producing O(3P can be entirely neglected in atmospheric kinetic modeling calculations. A further result of this study is an expression of the relative quantum yields as a function of temperature for the chemiluminescence reactions (kCL1C2H + O(1D → CH(A + CO and (kCL2C2H + O(3P → CH(A + CO, both followed by CH(A → CH(X + hν, as kCL1(T/kCL2(T=(32.8T−3050/(6.29T+398.

  4. Spectroscopy of actinium-215 and (p,t) studies of the stable palladium isotopes

    Science.gov (United States)

    Winkler, Ryan

    2009-12-01

    The study of both the microscopic and macroscopic structural evolution of the atomic nucleus is presented in this work. The excited states of the N = 126 isotone 215Ac were investigated at WNSL using the gas-filled recoil separator SASSYER. Recoil-decay tagging of the gamma rays corresponding to the decay of 215Ac after production via a fusion-evaporation reaction was made possible by using the redesigned SASSYER focal plane apparatus, including the addition of a pair of DSSDs and the multi-wire avalanche counter MACY. A number of transitions feeding the 29/2+ isomeric state corresponding to the ( ph49/2 )⊗(pii13/2) configuration were observed and tentatively assigned as decays from the high-spin 35/2 +, 39/2+, and 41/2+ states. Additionally, the decay from the low-lying 13/2+ state, corresponding to a pii13/2 quasiparticle excitation, was observed at 859 keV. This excitation energy is consistent with the systematics of the lighter N = 126 isotones suggesting a decrease in the energy gap between the pih9/2 and pi i13/2 orbitals. High-resolution (p,t) spectroscopy of the stable, even-even Palladium isotopes was performed in the search for signatures of quantum phase transitional behavior. A total of 54 previously unidentified 0+, 2 +, and 4+ states below an excitation energy of 3.5 MeV were discovered in this experiment. No enhancement of the 0+ level density, a signature of first-order phase transitions in nuclei, was observed in the studied isotopes. A theoretical description of the population strengths of excited 0+ states in two-nucleon transfer reactions was investigated within the framework of the IBM. These studies reveal that an enhanced population strength is not exclusive to regions of shape-coexistence but rather is a measure of the magnitude of the "change of structure" from the initial to residual nucleus.

  5. Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix.

    Science.gov (United States)

    Mastren, Tara; Radchenko, Valery; Owens, Allison; Copping, Roy; Boll, Rose; Griswold, Justin R; Mirzadeh, Saed; Wyant, Lance E; Brugh, Mark; Engle, Jonathan W; Nortier, Francois M; Birnbaum, Eva R; John, Kevin D; Fassbender, Michael E

    2017-08-15

    A new method has been developed for the isolation of (223,224,225)Ra, in high yield and purity, from a proton irradiated (232)Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of (223,224,225)Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.

  6. Inertial Confinement fusion targets

    Science.gov (United States)

    Hendricks, C. D.

    1982-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  7. Target Window Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    The target window design implemented and tested in experiments at ANL have performed without failure for the available beam of 6 mm FWHM on a 12 mm diameter target. However, scaling that design to a 25 mm diameter target size for a 12 mm FWHM beam has proven problematic. Combined thermal and mechanical (pressure induced) stresses and strains are too high to maintain the small coolant gaps and provide adequate fatigue lifetime.

  8. The ISOLDE target robots

    CERN Multimedia

    Maximilein Brice

    2002-01-01

    ISOLDE targets need to be changed frequently, around 80 times per year. The high radiation levels do not permit this to be done by human hands and the target changes are effected by 2 industrial robots (picture _01). On the left, in the distance, the front-end of the GPS (General Purpose Separator) is seen, while the HRS (High Resolution Separator) is at the right. Also seen are the doors to the irradiated-target storage.

  9. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  10. Target Assembly Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Target Assembly Facility integrates new armor concepts into actual armored vehicles. Featuring the capability ofmachining and cutting radioactive materials, it...

  11. Analysis of the 227 bp short interspersed nuclear element (SINE) insertion of the promoter of the myostatin (MSTN) gene in different horse breeds.

    Science.gov (United States)

    Dall'Olio, Stefania; Scotti, Emilio; Fontanesi, Luca; Tassinari, Marco

    2014-01-01

    The myostatin (MSTN) gene encodes a protein known to be a negative regulator of muscle mass in mammalian species. Different polymorphisms of the horse (Equus caballus) MSTN gene have been identified, including single nucleotide polymorphisms and a short interspersed nuclear element (SINE) insertion of 227 bp within the promoter of the gene. The SINE insertion has been associated with performance traits in Thoroughbred racehorses and it was proposed as a predictor of optimum racing distance. The aims of this study were to perform in silico analysis to identify putative gains or abrogation of transcription-factor binding sites (TFBSs) generated by the SINE allele of the promoter and to analyse the frequency of the SINE insertion in horses used for racing (gallop and trot) and other purposes. The SINE insertion was genotyped in 227 horses from 10 breeds belonging to different morphological types (brachimorphic, mesomorphic, meso-dolichomorphic and dolichomorphic). The presence of the insertion was confirmed in the Quarter Horse (SINE allele frequency of 0.81) and in the Thoroughbred (0.51), whereas the SINE allele did not segregate in any of the other analysed breeds. As the SINE MSTN gene polymorphism may be population or breed specific, it is not a useful marker for association studies in all breeds.

  12. Analysis of the 227 bp short interspersed nuclear element (SINE insertion of the promoter of the myostatin (MSTN gene in different horse breeds

    Directory of Open Access Journals (Sweden)

    Stefania Dall'Olio

    2014-09-01

    Full Text Available The myostatin (MSTN gene encodes a protein known to be a negative regulator of muscle mass in mammalian species. Different polymorphisms of the horse (Equus caballus MSTN gene have been identified, including single nucleotide polymorphisms and a short interspersed nuclear element (SINE insertion of 227 bp within the promoter of the gene. The SINE insertion has been associated with performance traits in Thoroughbred racehorses and it was proposed as a predictor of optimum racing distance. The aims of this study were to perform in silico analysis to identify putative gains or abrogation of transcription-factor binding sites (TFBSs generated by the SINE allele of the promoter and to analyse the frequency of the SINE insertion in horses used for racing (gallop and trot and other purposes. The SINE insertion was genotyped in 227 horses from 10 breeds belonging to different morphological types (brachimorphic, mesomorphic, meso-dolichomorphic and dolichomorphic. The presence of the insertion was confirmed in the Quarter Horse (SINE allele frequency of 0.81 and in the Thoroughbred (0.51, whereas the SINE allele did not segregate in any of the other analysed breeds. As the SINE MSTN gene polymorphism may be population or breed specific, it is not a useful marker for association studies in all breeds.

  13. Target visibility for multiple maneuvering target tracking

    Science.gov (United States)

    Sabordo, Madeleine G.; Aboutanios, Elias

    2015-05-01

    We present a recursion of the probability of target visibility and its applications to analysis of track life and termination in the context of Global Nearest Neighbour (GNN) approach and Probability Hypothesis Density (PHD) filter. In the presence of uncertainties brought about by clutter; decisions to retain a track, terminate it or initialise a new track are based on probability, rather than on distance criterion or estimation error. The visibility concept is introduced into a conventional data-association-oriented multitarget tracker, the GNN; and a random finite set based-tracker, the PHD filter, to take into account instances when targets become invisible or occluded by obstacles. We employ the natural logarithmof the Dynamic Error Spectrum to assess the performance of the trackers with and without probability of visibility incorporated. Simulation results show that the performance of the GNN tracker with visibility concept incorporated is significantly enhanced.

  14. Frozen spin targets

    CERN Document Server

    Parsons, A S L

    1976-01-01

    Describes six projects which use the frozen-spin principle: Helium-3 R.M.S. and longitudinally polarized frozen spin targets at Rutherford Laboratory, and the frozen spin targets at KEK, Saclay and the one used by the CERN-Helsinki collaboration. (7 refs).

  15. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  16. Strategic Targeted Advertising

    NARCIS (Netherlands)

    A. Galeotti; J.L. Moraga-Gonzalez (José Luis)

    2003-01-01

    textabstractWe present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit

  17. Segmented Target Design

    Science.gov (United States)

    Merhi, Abdul Rahman; Frank, Nathan; Gueye, Paul; Thoennessen, Michael; MoNA Collaboration

    2013-10-01

    A proposed segmented target would improve decay energy measurements of neutron-unbound nuclei. Experiments like this have been performed at the National Superconducting Cyclotron Laboratory (NSCL) located at Michigan State University. Many different nuclei are produced in such experiments, some of which immediately decay into a charged particle and neutron. The charged particles are bent by a large magnet and measured by a suite of charged particle detectors. The neutrons are measured by the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). With the current target setup, a nucleus in a neutron-unbound state is produced with a radioactive beam impinged upon a beryllium target. The resolution of these measurements is very dependent on the target thickness since the nuclear interaction point is unknown. In a segmented target using alternating layers of silicon detectors and Be-targets, the Be-target in which the nuclear reaction takes place would be determined. Thus the experimental resolution would improve. This poster will describe the improvement over the current target along with the status of the design. Work supported by Augustana College and the National Science Foundation grant #0969173.

  18. The CNGS target

    CERN Multimedia

    Patrice Loïez

    2005-01-01

    The CERN Neutrinos to Gran Sasso (CNGS) target ‘magazine’ of five target units. Each unit contains a series of 10-cm long graphite rods distributed over a length of 2 m. It is designed to maximize the number of secondary particles produced and hence the number of neutrinos. One unit is used at a time to prevent over heating.

  19. Targeted therapy in lymphoma

    Directory of Open Access Journals (Sweden)

    Cavalli Franco

    2010-11-01

    Full Text Available Abstract Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.

  20. Targets and teamwork

    DEFF Research Database (Denmark)

    Skinner, Timothy C; Lange, Karin S; Hoey, Hilary

    2017-01-01

    with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. Conclusions: The diabetes care....... Research Design and Methods: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed...... questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. Results: Totally 1113 (53% male) children (mean age 8.0±2.1years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial...

  1. Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) following whole-body exposure.

    Science.gov (United States)

    Emmen, H H; Hoogendijk, E M; Klöpping-Ketelaars, W A; Muijser, H; Duistermaat, E; Ravensberg, J C; Alexander, D J; Borkhataria, D; Rusch, G M; Schmit, B

    2000-08-01

    HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean

  2. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing of stainless steel. At the entrance to the target assembly was a scintillator screen, imprinted with circles every 5 mm in radius, which allowed to precisely aim the 26 GeV high-intensity proton beam from the PS onto the centre of the target rod. The scintillator screen was a 1 mm thick plate of Cr-doped alumina. See also 7903034 and 7905091.

  3. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

    Full Text Available This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio. However, target price accuracy is positively related to the level of detail of each report, company size and the reputation of the investment bank. The potential conflicts of interests between an analyst and a covered company do not bias forecast accuracy.

  4. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available This research describes a quantitative methodology for deriving optimal exploration target zones based on a probabilistic mineral prospectivity map. In order to arrive at out objective, we provide a plausible answer to the following question: "Which...

  5. Delays in thick targets

    CERN Document Server

    Bennett, J R J

    2002-01-01

    The delays in the emission of radioactive particles from a thick target bombarded by high-energy protons is discussed in relation to the basic physical processes of diffusion and effusion through the target and ioniser. The delay time, relative to the decay time, is crucial to the efficiency of particle release at the exit of the ioniser. The principles of minimizing the delay times are discussed with reference to a mathematical model of the process, and some experimental examples are given.

  6. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  7. Burglar Target Selection

    Science.gov (United States)

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  8. The Sinuous Target

    Energy Technology Data Exchange (ETDEWEB)

    Zwaska, R. [Fermilab

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  9. Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) following whole-body exposure

    NARCIS (Netherlands)

    Emmen, H.H.; Hoogendijk, E.M.G.; Klöpping-Ketelaars, W.A.A.; Muijser, H.; Duistermaat, E.; Ravensberg, J.C.; Alexander, D.J.; Borkhataria, D.; Rusch, G.M.; Schmit, B.

    2000-01-01

    HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal

  10. Setting reference targets

    Energy Technology Data Exchange (ETDEWEB)

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets.

  11. Targeted Therapy of CLL.

    Science.gov (United States)

    Al-Sawaf, Othman; Fischer, Kirsten; Eichhorst, Barbara; Hallek, Michael

    2016-01-01

    The landscape of chronic lymphocytic leukemia (CLL) has undergone profound changes in the past years. First, the addition of CD20-targeting antibodies to conventional chemotherapy has improved the therapeutic outcome in the majority of CLL patients. Since the establishment of the critical role of the B cell receptor signaling pathway in the pathogenesis of CLL, several agents have been developed to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors, have both become available for CLL therapy in the first and second line. Additionally, the observation of high expression levels of the anti-apoptotic mitochondrial protein Bcl-2 in CLL has led to the development of venetoclax, a BH3 mimetic compound that inhibits Bcl-2 and has shown high efficacy in CLL. This short review summarizes preclinical and clinical data on currently available agents in CLL and provides an outlook on upcoming new challenges in the targeted therapy of CLL. © 2016 S. Karger GmbH, Freiburg.

  12. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

    2014-01-01

    Within the European Union (EU) a paradigm shift is currently occurring in the waste sector, where EU waste directives and national waste strategies are placing emphasis on resource efficiency and recycling targets. The most recent Danish resource strategy calculates a national recycling rate of 22......% for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...... the existing technological, organizational and legislative frameworks may affect recycling activities. The results of the analysis show that with current best practice recycling rates, the 50% recycling rate cannot be reached without recycling of household biowaste. It also shows that all Danish municipalities...

  13. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available , Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results Optimal Exploration Target Zones Pravesh Debba1, Emmanual M.J. Carranza2, Alfred Stein2, Freek D. van der Meer2 1CSIR, Logistics... and Quantitative Methods, CSIR Built Environment 2International Institute for Geo-Information Science and Earth Observation (ITC), Hengelosestraat 99, P.O. Box 6, 7500AA Enschede, The Netherlands Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer...

  14. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long (actually a row of 11 rods, each 1 cm long) and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing made of stainless steel. The casing had fins for forced-air cooling. In this picture, the 26 GeV high-intensity beam from the PS enters from the right, where a scintillator screen, with circles every 5 mm in radius, permits precise aim at the target centre. See also 7903034 and 7905094.

  15. Aquaporin-2 membrane targeting

    DEFF Research Database (Denmark)

    Olesen, Emma T B; Fenton, Robert A

    2017-01-01

    The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis...

  16. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  17. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  18. Target Heart Rates

    Science.gov (United States)

    ... is your level of intensity? When is the best time of day to work out? Target Heart Rates Warm Up, Cool Down See More >> Getting Active Getting Started - Tips for Long-term Exercise Success Get Moving: Easy Tips to Get Active! ...

  19. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  20. Target Chamber Manipulator

    Science.gov (United States)

    Tantillo, Anthony; Watson, Matthew

    2015-11-01

    A system has been developed to allow remote actuation of sensors in a high vacuum target chamber used with a particle accelerator. Typically, sensors of various types are placed into the target chamber at specific radial and angular positions relative to the beam line and target. The chamber is then evacuated and the experiments are performed for those sensor positions. Then, the chamber is opened, the sensors are repositioned to new angles or radii, and the process is repeated, with a separate pump-down cycle for each set of sensor positions. The new sensor positioning system allows scientists to pre-set the radii of up to a dozen sensors, and then remotely actuate their angular positions without breaking the vacuum of the target chamber. This reduces the time required to reposition sensors from 6 hours to 1 minute. The sensors are placed into one of two tracks that are separately actuated using vacuum-grade stepping motors. The positions of the sensors are verified using absolute optical rotary encoders, and the positions are accurate to 0.5 degrees. The positions of the sensors are electronically recorded and time-stamped after every change. User control is through a GUI using LabVIEW.

  1. Active Target Simulation

    Science.gov (United States)

    Smith, Nathan; Draznik, Peter; Frank, Nathan

    2012-10-01

    We have simulated an existing experimental design to determine the resolution improvement upon energy measurements of neutron unbound nuclei. A number of experiments of this type have been performed at the National Superconducting Cyclotron Laboratory (NSCL), located at Michigan State University. An excited nucleus is typically produced with a radioactive beam interacting with a passive Beryllium target. Many different nuclei are produced in experiment, each of which immediately decays into a charged particle and neutron. The charged particles are detected and the neutrons interact in scintillation detectors such as the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). In our simulation, we have constructed an active target that provides additional information such that the point of nuclear interaction within the target may be determined. This information improves the resolution in decay energy measurements of neutron unbound isotopes. This presentation will cover some aspects of the simulation process, as well as showing some of the results that demonstrate the simulated improvement over a passive target.

  2. Ac, La, and Ce radioimpurities in {sup 225}Ac produced in 40-200 MeV proton irradiations of thorium

    Energy Technology Data Exchange (ETDEWEB)

    Engle, Jonathan W.; Ballard, Beau D. [Los Alamos National Laboratory, NM (United States); Weidner, John W. [Air Force Institute of Technology, Wright Patterson Air Force Base, OH (United States); and others

    2014-10-01

    Accelerator production of {sup 225}Ac addresses the global supply deficiency currently inhibiting clinical trials from establishing {sup 225}Ac's therapeutic utility, provided that the accelerator product is of sufficient radionuclidic purity for patient use. Two proton activation experiments utilizing the stacked foil technique between 40 and 200 MeV were employed to study the likely co-formation of radionuclides expected to be especially challenging to separate from {sup 225}Ac. Foils were assayed by nondestructive γ-spectroscopy and by α-spectroscopy of chemically processed target material. Nuclear formation cross sections for the radionuclides {sup 226}Ac and {sup 227}Ac as well as lower lanthanide radioisotopes {sup 139}Ce, {sup 141}Ce, {sup 143}Ce, and {sup 140}La whose elemental ionic radii closely match that of actinium were measured and are reported. The predictions of the latest MCNP6 event generators are compared with measured data, as they permit estimation of the formation rates of other radionuclides whose decay emissions are not clearly discerned in the complex spectra collected from {sup 232}Th(p,x) fission product mixtures. (orig.)

  3. Physics of polarized targets

    CERN Document Server

    Niinikoski, Tapio

    2014-01-01

    For developing, building and operating solid polarized targets we need to understand several fields of physics that have seen sub stantial advances during the last 50 years. W e shall briefly review a selection of those that are important today. These are: 1) quantum statistical methods to describe saturation and relaxation in magnetic resonance; 2) equal spin temperature model for dy namic nuclear polarization; 3 ) weak saturation during NMR polarization measurement; 4 ) refrigeration using the quantum fluid properties of helium isotopes. These, combined with superconducting magnet technologies, permit today to reach nearly complete pola rization of almost any nuclear spins. Targets can be operated in frozen spin mode in rather low and inhomogeneous field of any orientation, and in DNP mode in beams of high intensity. Beyond such experiments of nuclear and particle physics, applications a re also emerging in macromolecular chemistry and in magnetic resonance imaging. This talk is a tribute to Michel Borghini...

  4. Emerging Targets in Photopharmacology.

    Science.gov (United States)

    Lerch, Michael M; Hansen, Mickel J; van Dam, Gooitzen M; Szymanski, Wiktor; Feringa, Ben L

    2016-09-05

    The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring "smart" molecular design ultimately to the realm of clinical use. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Inflation Targeting: Provisional Results

    Directory of Open Access Journals (Sweden)

    Cerna, Silviu

    2010-06-01

    Full Text Available Inflation targeting monetary policy framework that requires the central bank to achieve a low inflation has contributed to price stability in industrialized countries. As well as the other developing countries, ex communist countries have also tried to apply this strategy, which was susceptible to increase monetary policy transparency and to determine authorities to make necessary reforms in order to pass from a planned to a market economy. In Romania, inflation targeting has contributed, to a large extent, to price increase smoothening, without affecting economic growth. Knowing the factors that have determined this unquestionable success allows for not only understanding the Romanian transition process, but also draw some useful conclusions in view of the necessary actions for adopting the euro.

  6. Foucault on targets.

    Science.gov (United States)

    Lynch, John

    2004-01-01

    This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

  7. Antibodies Targeting EMT

    Science.gov (United States)

    2017-10-01

    VLDL uptake and redistribution of lipids to cells for energy metabolism and cell signaling. ApoE overexpression has shown to be associated with a...involved in testosterone and estradiol biosynthesis, as well as prostaglandin F synthesis and has previously been implicated in cancer progression, AKR1C2...is involved in androgen metabolism and is a potential drug target for prostate cancer. AKR1C4 is involved in bile acid synthesis but has not yet

  8. Explosive Target Balances

    OpenAIRE

    Potrafke, Niklas; Reischmann, Markus

    2013-01-01

    Using the new unit root test by Phillips et al. (2011) we show that the Target balances of the German Bundesbank have been exploding from the beginning of 2009 to the beginning of 2013. By implementing a full-allotment policy and reducing the required minimum quality of collaterals in October 2008, the European Central Bank (ECB) refinanced credits in the GIIPS countries to a large extent. Private capital flowed out of the GIIPS countries (Greece, Italy, Ireland, Portugal and Spain), and the ...

  9. Implementing Target Value Design.

    Science.gov (United States)

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  10. Inflation targeting and core inflation

    OpenAIRE

    Julie Smith

    2005-01-01

    This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

  11. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  12. Meeting the Aichi targets

    DEFF Research Database (Denmark)

    Funk, Stephan M; Conde, Dalia Amor; Lamoreux, John

    2017-01-01

    &s), is an excellent opportunity to achieve the Aichi 2020 Targets T11 (protected areas) and T12 (preventing species extinctions). AZE taxa have small, single-site populations that are especially vulnerable to human-induced extinctions, particularly for the many amphibians. We show that AZEs&s can be protected...... feasibly and cost-effectively, but action is urgent. We argue that the Alliance, whose initial main aim was to identify AZEs&s, must be followed up by a second-generation initiative that directs and co-ordinates AZE conservation activities on the ground. The prominent role of zoos, conservation NGOs...

  13. Polarized scintillator targets

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2000-05-01

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as "live" polarized targets in nuclear physics experiments.

  14. Polarized scintillator targets

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den E-mail: vandenbrandt@psi.ch; Bunyatova, E.I.; Hautle, P.; Konter, J.A.; Mango, S

    2000-05-21

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as 'live' polarized targets in nuclear physics experiments.

  15. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    achieve this goal, we cultured high-invasive prostate cancer PC3 cells and treated them with the drugs/inhibitors that were proposed to target WASF3...groups (treated by DMSO), either treated by 100 μM CYT997 or 10 μM Dasatinib suppressed the cells to spread throughout the fish body (Fig. 4). As...have scr eened t he e f fect s o f mor e t han 40 drugs on invasion using cul tur ed prost ate cancer cells and f ound t hat tar geting multiple

  16. Optimal Systolic Blood Pressure Target After SPRINT: Insights from a Network Meta-Analysis of Randomized Trials.

    Science.gov (United States)

    Bangalore, Sripal; Toklu, Bora; Gianos, Eugenia; Schwartzbard, Arthur; Weintraub, Howard; Ogedegbe, Gbenga; Messerli, Franz H

    2017-06-01

    The optimal on-treatment blood pressure (BP) target has been a matter of debate. The recent SPRINT trial showed significant benefits of a BP target of meta-analysis. Seventeen trials that enrolled 55,163 patients with 204,103 patient-years of follow-up were included. There was a significant decrease in stroke (rate ratio [RR] 0.54; 95% confidence interval [CI], 0.29-1.00) and myocardial infarction (RR 0.68; 95% CI, 0.47-1.00) with systolic BP <120 mm Hg (vs <160 mm Hg). Sensitivity analysis using achieved systolic BP showed a 72%, 97%, and 227% increase in stroke with systolic BP of <140 mm Hg, <150 mm Hg, and <160 mm, respectively, when compared with systolic BP <120 mm Hg. There was no difference in death, cardiovascular death, or heart failure when comparing any of the BP targets. However, the point estimate favored lower BP targets (<120 mm Hg, <130 mm Hg) when compared with higher BP targets (<140 mm Hg or <150 mm Hg). BP targets of <120 mm Hg and <130 mm Hg ranked #1 and #2, respectively, as the most efficacious target. There was a significant increase in serious adverse effects with systolic BP <120 mm Hg vs <150 mm Hg (RR 1.83; 95% CI, 1.05-3.20) or vs <140 mm Hg (RR 2.12; 95% CI, 1.46-3.08). BP targets of <140 mm Hg and <150 mm Hg ranked #1 and #2, respectively, as the safest target for the outcome of serious adverse effects. Cluster plots for combined efficacy and safety showed that a systolic BP target of <130 mm Hg had optimal balance between efficacy and safety. In patients with hypertension, a on-treatment systolic BP target of <130 mm Hg achieved optimal balance between efficacy and safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Targeting Nuclear Thymidylate Biosynthesis

    Science.gov (United States)

    Chon, James; Stover, Patrick J.; Field, Martha S.

    2016-01-01

    Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA synthesis and proper cell division, and therefore has been an attractive therapeutic target. Folate analogues, known as antifolates, and nucleotide analogs that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway and are commonly used in cancer treatment. In this review, we examine the mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP synthesis inhibitors, function in cancer treatment in light of emerging evidence that dTMP synthesis occurs in the nucleus. Nuclear localization of the de novo dTMP synthesis pathway requires modification of the pathway enzymes by the small ubiquitin-like modifier (SUMO) protein. SUMOylation is required for nuclear localization of the de novo dTMP biosynthesis pathway, and disruption in the SUMO pathway inhibits cell proliferation in several cancer models. We summarize evidence that the nuclear localization of the dTMP biosynthesis pathway is a critical factor in the efficacy of antifolate-based therapies that target dTMP synthesis. PMID:27876557

  18. Targeted corneal transplantation.

    Science.gov (United States)

    Jhanji, Vishal; Mehta, Jod S; Sharma, Namrata; Sharma, Bhavana; Vajpayee, Rasik B

    2012-07-01

    Corneal transplantation surgery has moved from an era of conventional penetrating keratoplasty to selective replacement of the diseased corneal layer with complementary healthy donor corneal tissue. Anterior lamellar transplantation surgeries do not involve replacement of corneal endothelium, consequently eliminating the occurrence of endothelial rejection. Similarly, in diseases affecting the corneal endothelium, selective replacement with a lamellar lenticule bearing healthy endothelium provides better outcomes in terms of ocular surface, lesser astigmatism and quick visual recovery. In addition to the advantages of enhanced surgical outcomes, targeted corneal transplantation allows the use of one donor cornea for more than one recipient, thereby offering a viable solution to the problem of paucity of donor corneas. Evolving techniques of corneal transplantation have enabled better utilization of donor corneal tissue. Anterior lamellar as well as endothelial keratoplasty surgeries have become first-choice surgeries in appropriately selected cases. This review briefly discusses some of these novel surgical techniques. A better understanding of targeted corneal transplantation would lead to adaptation of the concept of component corneal surgery. This would further enable the corneal surgeons to circumvent the problem of donor corneal shortage especially in the developing world.

  19. Fixed target beams

    CERN Document Server

    Kain, V; Cettour-Cave, S; Cornelis, K; Fraser, M A; Gatignon, L; Goddard, B; Velotti, F

    2017-01-01

    The CERN SPS (Super Proton Synchrotron) serves asLHC injector and provides beam for the North Area fixedtarget experiments. At low energy, the vertical acceptancebecomes critical with high intensity large emittance fixed tar-get beams. Optimizing the vertical available aperture is a keyingredient to optimize transmission and reduce activationaround the ring. During the 2016 run a tool was developed toprovide an automated local aperture scan around the entirering.The flux of particles slow extracted with the1/3inte-ger resonance from the Super Proton Synchrotron at CERNshould ideally be constant over the length of the extractionplateau, for optimum use of the beam by the fixed target ex-periments in the North Area. The extracted intensity is con-trolled in feed-forward correction of the horizontal tune viathe main SPS quadrupoles. The Mains power supply noiseat 50 Hz and harmonics is also corrected in feed-forwardby small amplitude tune modulation at the respective fre-quencies with a dedicated additional quad...

  20. Old Drug, New Target

    Science.gov (United States)

    Andrews, William J.; Panova, Tatiana; Normand, Christophe; Gadal, Olivier; Tikhonova, Irina G.; Panov, Konstantin I.

    2013-01-01

    Transcription by RNA polymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear. It has long been thought that inhibition of Top2 is the main reason behind the drugs antiproliferative effects. Here we report that a number of the ellipticines, including 9-hydroxyellipticine, are potent and specific inhibitors of Pol-I transcription, with IC50 in vitro and in cells in the nanomolar range. Essentially, the drugs did not affect Pol-II and Pol-III transcription, demonstrating a high selectivity. We have shown that Pol-I inhibition occurs by a p53-, ATM/ATR-, and Top2-independent mechanism. We discovered that the drug influences the assembly and stability of preinitiation complexes by targeting the interaction between promoter recognition factor SL1 and the rRNA promoter. Our findings will have an impact on the design and development of novel therapeutic agents specifically targeting ribosome biogenesis. PMID:23293027

  1. Quantum state targeting

    Science.gov (United States)

    Rudolph, Terry; Spekkens, Robert W.

    2004-11-01

    We introduce a primitive for quantum cryptography that we term “state targeting.” We show that increasing one’s probability of success in this task above a minimum amount implies an unavoidable increase in the probability of a particular kind of failure. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We solve various optimization problems for state targeting that are useful for the security analysis of two-party cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater’s ability to bias the outcome of the protocol, but also for a different notion of security that arises only in the quantum context, that of cheat sensitivity. Finally, our analysis leads to some interesting secondary results, namely, a generalization of Uhlmann’s theorem and an operational interpretation of the fidelity between two mixed states.

  2. Target Housing Material Options

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    With gas cooling, heat transfer coefficients are low compared to water. The benefit of gas from a heat transfer point of view is that there is really no upper temperature limit for the coolant, as compared to water, which is limited ultimately by the critical point, and in practice the critical heat flux. In our case with parallel flow channels, water is limited to even lower operating limits by nucleate boiling. So gas can get as hot as the containment material will allow, but to get the density and heat transfer up to something reasonable, we must also increase pressure, thus increasing stress on the containment, namely the front and back faces. We are designing to ASME BPVC, which, for most materials allows a maximum stress of UTS/3. So we want the highest possible UTS. For reference, the front face stress in the 12 mm target at 300 psi was about 90 MPa. The inconel 718 allowable stress at 900°C is 1/3 of 517 or 172 MPa. So we are in a very safe place, but the uTS is dropping rapidly with temperature above 900°C. As we increase target diameter, the challenge will be to keep the stress down. We are probably looking at keeping the allowable at or above the present value, and at as high a temperature as possible.

  3. Targeting adipose tissue

    Directory of Open Access Journals (Sweden)

    Haas Bodo

    2012-10-01

    Full Text Available Abstract Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT is generally known and stores excess energy in the form of triacylglycerol (TG, insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP. The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET, however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs, activators of peroxisome proliferator-activated receptor γ (PPARγ a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  4. Targeting adipose tissue.

    Science.gov (United States)

    Haas, Bodo; Schlinkert, Paul; Mayer, Peter; Eckstein, Niels

    2012-10-27

    Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor γ (PPARγ) a 'master' regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  5. Low intensity beam target unit

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    This is a wheel fitted with many targets around its periphery (each with three longitudinally arranged thin rods) of which one is placed into the beam via a rotation of the wheel. Upstream of each target is placed a luminescent screen, aligbed on each target axis and viewed with a TV camera, to make sure that one is hitting the target. This target unit was probably used to study target's behaviour (like beam heating). Gualtiero Del Torre stands on the left, Pierre Gerdil on the right.

  6. Issues in Target Tracking

    Science.gov (United States)

    2010-05-01

    simulations we take as ground truth that the target moves at 10m/s heading west and 5m/s heading north, starting from ( 5000m , 35000m). The emitted frequency is... runs , the estimated initial and final positions fall into the 99% confidence region. −1 −0.8 −0.6 −0.4 −0.2 0 0.2 0.4 0.6 0.8 1 x 10 4 0 0.5 1 1.5 2 2.5...position of trajectories. “F”: final position of trajectories. Right: The true and estimated trajectories from 100 Monte Carlo runs for Johnson noise

  7. Bradycardia During Targeted Temperature Management

    DEFF Research Database (Denmark)

    Thomsen, Jakob Hartvig; Nielsen, Niklas; Hassager, Christian

    2016-01-01

    OBJECTIVES: Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought...... to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. DESIGN: Post hoc analysis of a prospective randomized study. SETTING: Thirty-six ICUs in 10 countries. PATIENTS......: We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. INTERVENTIONS: Targeted...

  8. Characterization of solid hydrogen targets

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, M.C. [British Columbia Univ., Vancouver, BC (Canada); Bailey, J.M.; Mulhauser, F. [Chester Technology (United Kingdom); Beer, G.A.; Douglas, J.L.; Knowles, P.E.; Maier, M.; Mason, G.R.; Olin, A.; Porcelli, T.A. [Victoria Univ., BC (Canada); Beveridge, J.L.; Marshall, G.M. [British Columbia Univ., Vancouver, BC (Canada). TRIUMF Facility; Huber, T.M. [Gustavus Adolphus Coll., St. Peter, MN (United States); Jacot-Guillarmod, R. [Fribourg Univ. (Switzerland); Kammel, P. [Lawrence Berkeley Lab., CA (United States); Kim, S.K. [Jeonbuk National Univ., Jeonju City (Korea, Republic of); Kunselman, A.R. [Wyoming Univ., Laramie, WY (United States); Martoff, C.J. [Temple Univ., Philadelphia, PA (United States); Petitjean, C. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Zmeskal, J. [Oesterreichische Akademie der Wissenschaften, Vienna (Austria)

    1996-10-01

    In experiments using the TRIUMF solid hydrogen target system, the knowledge of the target thickness and uniformity is often essential in order to extract physical parameters from the data. We have characterized the thickness and uniformity of frozen targets using the energy loss of alpha particles. An accuracy of {approx}5% was achieved, a limit imposed by the uncertainty in the stopping powers. The details of the method are described, and the thickness calibration of the target is presented. (orig.). 11 refs.

  9. Solid tumor-targeted infiltrating cytotoxic T lymphocytes retained by a superantigen fusion protein.

    Directory of Open Access Journals (Sweden)

    Jialin Sun

    Full Text Available Successful immune-mediated regression of solid tumors is difficult because of the small number of cytotoxic T lymphocytes (CTLs that were traffic to the tumor site. Here, the targeting of tumor-specific infiltrating CTLs was dependent on a fusion protein consisting of human epidermal growth factor (EGF and staphylococcal enterotoxin A (SEA with the D227A mutation. EGF-SEA strongly restrained the growth of murine solid sarcoma 180 (S180 tumors (control versus EGF-SEA, mean tumor weight: 1.013 versus 0.197 g, difference  = 0.816 g. In mice treated with EGF-SEA, CD4+, CD8+ and SEA-reactive T lymphocytes were enriched around the EGFR expressing tumor cells. The EGF receptors were potentially phosphorylated by EGF-SEA stimulation and the fusion protein promoted T cells to release the tumoricidal cytokines interferon-γ (IFN-γ and tumor necrosis factor-α (TNF-α. Intratumoral CTLs secreted cytolytic pore-forming perforins and granzyme B proteins near the surface of carcinomas, causing the death of many tumor cells. We additionally show that labeled EGF-SEA was directly targeted to the tumor tissue after intravenous (i.v. injection. The findings demonstrate that antibody-like EGF-SEA plays an important role in arresting CTLs in the solid tumor site and has therapeutic potential as a tumor-targeting agent.

  10. Target noise in overlay metrology

    Science.gov (United States)

    Seligson, Joel L.; Adel, Mike E.; Izikson, Pavel; Levinski, Vladimir; Yaffe, Dan

    2004-05-01

    We have developed a method for calculating the statistical effects of spatial noise on the overlay measurement extracted from a given overlay target. The method has been applied to two kinds of overlay targets on three process layers, and the new metric, Target Noise, has been shown to correlate well to the random component of Overlay Mark Fidelity. A significant difference in terms of robustness has been observed between AIM targets and conventional Frame-in-Frame targets. The results fit well into the spatial noise hierarchy presented in this paper.

  11. EURISOL High Power Targets

    CERN Document Server

    Kadi, Y; Lindroos, M; Ridikas, D; Stora, T; Tecchio, L; CERN. Geneva. BE Department

    2009-01-01

    Modern Nuclear Physics requires access to higher yields of rare isotopes, that relies on further development of the In-flight and Isotope Separation On-Line (ISOL) production methods. The limits of the In-Flight method will be applied via the next generation facilities FAIR in Germany, RIKEN in Japan and RIBF in the USA. The ISOL method will be explored at facilities including ISAC-TRIUMF in Canada, SPIRAL-2 in France, SPES in Italy, ISOLDE at CERN and eventually at the very ambitious multi-MW EURISOL facility. ISOL and in-flight facilities are complementary entities. While in-flight facilities excel in the production of very short lived radioisotopes independently of their chemical nature, ISOL facilities provide high Radioisotope Beam (RIB) intensities and excellent beam quality for 70 elements. Both production schemes are opening vast and rich fields of nuclear physics research. In this article we will introduce the targets planned for the EURISOL facility and highlight some of the technical and safety cha...

  12. The target effect: visual memory for unnamed search targets.

    Science.gov (United States)

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

    Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

  13. Guidance and targeting for the Strategic Target System

    Science.gov (United States)

    White, John E.

    Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at intercontinental ballistic missile velocities. Mission objectives are achieved with a combination of guidance algorithms.

  14. 227 - 233_Yahaya_Antimicrobial

    African Journals Online (AJOL)

    pc

    the dental plaque and food from the teeth, assists suppressing halitosis, and delivers active ingredie. (most commonly fluoride) to help prevent tooth a gum disease called gingivitis (American Den. Association, 2010). A very significant proportion dental problem are due to microbial infection. Den problems are of three types, ...

  15. Oxide Fiber Targets at ISOLDE

    CERN Document Server

    Köster, U; Carminati, D; Catherall, R; Cederkäll, J; Correia, J G; Crepieux, B; Dietrich, M; Elder, K; Fedosseev, V; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Georg, U; Giles, T; Joinet, A; Jonsson, O C; Kirchner, R; Lau, C; Lettry, Jacques; Maier, H J; Mishin, V I; Oinonen, M; Peräjärvi, K; Ravn, H L; Rinaldi, T; Santana-Leitner, M; Wahl, U; Weissman, L

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process or by burning commercial gas lantern mantle cloth. In the future a beryllia fiber target could be used to produce...

  16. Therapeutic Targeting of Telomerase

    Directory of Open Access Journals (Sweden)

    Kathrin Jäger

    2016-07-01

    Full Text Available Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT, which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality. Thus, reversal of telomerase upregulation in tumor cells is a potential strategy to treat cancer. Natural and small-molecule telomerase inhibitors, immunotherapeutic approaches, oligonucleotide inhibitors, and telomerase-directed gene therapy are useful treatment strategies. Telomerase is more widely expressed than any other tumor marker. The low expression in normal tissues, together with the longer telomeres in normal stem cells versus cancer cells, provides some degree of specificity with low risk of toxicity. However, long term telomerase inhibition may elicit negative effects in highly-proliferative cells which need telomerase for survival, and it may interfere with telomere-independent physiological functions. Moreover, only a few hTERT molecules are required to overcome senescence in cancer cells, and telomerase inhibition requires proliferating cells over a sufficient number of population doublings to induce tumor suppressive senescence. These limitations may explain the moderate success rates in many clinical studies. Despite extensive studies, only one vaccine and one telomerase antagonist are routinely used in clinical work. For complete eradication of all subpopulations of cancer cells a simultaneous targeting of several mechanisms will likely be needed. Possible technical improvements have been proposed including the development of more specific inhibitors, methods to increase the efficacy of vaccination

  17. Target Acquisition Methodology Enhancement (TAME)

    Science.gov (United States)

    1989-03-01

    acquisition probability from COMINT, PCOM , against all communications type targets, is determined offline by a stochastic model for subsequent...of PN over all replications. F-4 f. Computes overall acquisition probability, PCOM , against all communications type targets as C: PCOM = (1. - PN...NNET where NNET denotes the number of nets which the target is in. F-6. TOTAL ACQUISITION PROBABILITY. With PNCj and PCOM computed as above, the

  18. Guidance system for laser targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  19. Targeted nanotechnology for cancer imaging.

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Targets and Secondary Beam Extraction

    Science.gov (United States)

    Noah, Etam

    2014-02-01

    Several applications make use of secondary beams of particles generated by the interaction of a primary beam of particles with a target. Spallation neutrons, bremsstrahlung photon-produced neutrons, radioactive ions and neutrinos are available to users at state-of-the-art facilities worldwide. Plans for even higher secondary beam intensities place severe constraints on the design of targets. This article reports on the main targetry challenges and highlights a variety of solutions for targetry and secondary beam extraction. Issues related to target station layout, instrumentation at the beam-target interface, safety and radioprotection are also discussed.

  1. Purification of radium-226 for the manufacturing of actinium-225 in a cyclotron for alpha-immunotherapy; Radium-Aufreinigung zur Herstellung von Actinium-225 am Zyklotron fuer die Alpha-Immuntherapie

    Energy Technology Data Exchange (ETDEWEB)

    Marx, Sebastian Markus

    2014-09-23

    The thesis describes the development of methods for the purification of Ra-226. The objective was to obtain the radionuclide in the quality that is needed to be used as starting material in the manufacturing process for Ac-225 via proton-irradiated Ra-226. The radionuclide has been gained efficiently out of huge excesses of impurities. The high purity of the obtained radium affords its use as staring material in a pharmaceutical manufacturing process.

  2. Achieving Plant CRISPR Targeting that Limits Off-Target Effects

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Wolt

    2016-11-01

    Full Text Available The CRISPR-Cas9 system (clustered regularly interspaced short palindromic repeats with associated Cas9 protein has been used to generate targeted changes for direct modification of endogenous genes in an increasing number of plant species; but development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome. Assessing the specificity of CRISPR-Cas9 for increasing editing efficiency as well as the potential for unanticipated downstream effects from off-target mutations is an important regulatory consideration for agricultural applications. Increasing genome-editing specificity entails developing improved design methods that better predict the prevalence of off-target mutations as a function of genome composition and design of the engineered ribonucleoprotein (RNP. Early results from CRISPR-Cas9 genome editing in plant systems indicate that the incidence of off-target mutation frequencies is quite low; however, by analyzing CRISPR-edited plant lines and improving both computational tools and reagent design, it may be possible to further decrease unanticipated effects at potential mismatch sites within the genome. This will provide assurance that CRISPR-Cas9 reagents can be designed and targeted with a high degree of specificity. Improved and experimentally validated design tools for discriminating target and potential off-target positions that incorporate consideration of the designed nuclease fidelity and selectivity will help to increase confidence for regulatory decision making for genome-edited plants.

  3. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  4. Transverse target spin asymmetries on a proton target at COMPASS

    CERN Document Server

    Richter, Andreas

    2009-01-01

    Transversity and transverse momentum-dependent parton distribution functions (TMDs) are been measured in semi-inclusive deep inelastic scattering (SIDIS) by using a transversely polarized target at the COMPASS experiment. COMPASS is a fixed target experiment at the CERN M2 beamline, which provides a 160GeV/c polarized m+ beam. In the years 2002-2004 COMPASS has collected data with a transversely polarized deuteron 6LiD target. In 2007, COMPASS has used for the first time a proton NH3 target. To access transversity COMPASS has used three different quark polarimeters: the Collins effect, responsible for an azimuthal asymmetry in the single hadron distribution, azimuthal target spin asymmetries of charged hadron pairs and the transverse polarisation of L hyperons. Beside this also the Sivers asymmetry arising from the correlation between the transverse nucleon spin and the quark intrinsic transverse momentum was measured. European

  5. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  6. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this t...

  7. Saccadic adaptation to moving targets.

    Directory of Open Access Journals (Sweden)

    Katharina Havermann

    Full Text Available Saccades are so called ballistic movements which are executed without online visual feedback. After each saccade the saccadic motor plan is modified in response to post-saccadic feedback with the mechanism of saccadic adaptation. The post-saccadic feedback is provided by the retinal position of the target after the saccade. If the target moves after the saccade, gaze may follow the moving target. In that case, the eyes are controlled by the pursuit system, a system that controls smooth eye movements. Although these two systems have in the past been considered as mostly independent, recent lines of research point towards many interactions between them. We were interested in the question if saccade amplitude adaptation is induced when the target moves smoothly after the saccade. Prior studies of saccadic adaptation have considered intra-saccadic target steps as learning signals. In the present study, the intra-saccadic target step of the McLaughlin paradigm of saccadic adaptation was replaced by target movement, and a post-saccadic pursuit of the target. We found that saccadic adaptation occurred in this situation, a further indication of an interaction of the saccadic system and the pursuit system with the aim of optimized eye movements.

  8. Saccadic adaptation to moving targets.

    Science.gov (United States)

    Havermann, Katharina; Volcic, Robert; Lappe, Markus

    2012-01-01

    Saccades are so called ballistic movements which are executed without online visual feedback. After each saccade the saccadic motor plan is modified in response to post-saccadic feedback with the mechanism of saccadic adaptation. The post-saccadic feedback is provided by the retinal position of the target after the saccade. If the target moves after the saccade, gaze may follow the moving target. In that case, the eyes are controlled by the pursuit system, a system that controls smooth eye movements. Although these two systems have in the past been considered as mostly independent, recent lines of research point towards many interactions between them. We were interested in the question if saccade amplitude adaptation is induced when the target moves smoothly after the saccade. Prior studies of saccadic adaptation have considered intra-saccadic target steps as learning signals. In the present study, the intra-saccadic target step of the McLaughlin paradigm of saccadic adaptation was replaced by target movement, and a post-saccadic pursuit of the target. We found that saccadic adaptation occurred in this situation, a further indication of an interaction of the saccadic system and the pursuit system with the aim of optimized eye movements.

  9. Target recognition by wavelet transform

    CERN Document Server

    Li Zheng Dong; He Wu Liang; Pei Chun Lan; Peng Wen; SongChen; Zheng Xiao Dong

    2002-01-01

    Wavelet transform has an important character of multi-resolution power, which presents pyramid structure, and this character coincides the way by which people distinguish object from coarse to fineness and from large to tiny. In addition to it, wavelet transform benefits to reducing image noise, simplifying calculation, and embodying target image characteristic point. A method of target recognition by wavelet transform is provided

  10. ISOLDE target zone control room

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  11. Targeted marketing and public health.

    Science.gov (United States)

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

  12. Oxide fiber targets at ISOLDE

    DEFF Research Database (Denmark)

    Köster, U.; Bergmann, U.C.; Carminati, D.

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some...... contact points. The experience with various oxide fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils......, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process...

  13. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

    Denver, Troelz; Jørgensen, John Leif; Betto, Maurizio

    2003-01-01

    The key science instrument on the Bering satellite mission is a relative small telescope with an entrance aperture of 300 mm and a focal length between 500 and 1000 mm. The detection of potential targets is performed by one of the target scanning advanced stellar compasses (ASCs). This procedure...... results in a simple prioritized list of right ascension, declination, proper motion and intensity of each prospective target. The telescope itself has a dedicated ASC Camera Head Unit (CHU) mounted on the secondary mirror, largely co-aligned with the telescope. This CHU accurately determines the telescope......'s pointing direction. To achieve fast tracking over a large solid angle, the telescope pointing is achieved by means of a folding mirror in the optical pathway. When a prospective target approaches the telescope FOV, the ASC on the secondary will guide the folding mirror into position such that the target...

  14. High speed cryogenic monodisperse targets

    Science.gov (United States)

    Boukharov, A.; Vishnevkii, E.

    2017-11-01

    The basic possibility of creation of high speed cryogenic monodisperse targets is shown. According to calculations at input of thin liquid cryogenic jets with a velocity of bigger 100 m/s in vacuum the jets don’t manage to freeze at distance to 1 mm and can be broken into monodisperse drops. Drops due to evaporation are cooled and become granules. High speed cryogenic monodisperse targets have the following advantages: direct input in vacuum (there is no need for a chamber of a triple point chamber and sluices), it is possible to use the equipment of a cluster target, it is possible to receive targets with a diameter of D 100m/s), exact synchronization of the target hitting moment in a beam with the moment of sensors turning on.

  15. [Measurement of fluid compartments using electrical bioimpedance for assessment of target weight in hemodialysis patients].

    Science.gov (United States)

    Załuska, W; Jaroszyński, A; Bober, E; Małecka, T; Kozik, J; Ksiazek, A

    2000-01-01

    The prescription of optimal hydration status in hemodialysis patients remains a much disputed topic in dialysis treatment. In particular, assessment of the patients optimal weight ("target weight") poses considerable difficulties. Multifrequency bioimpedance spectroscopy analysis (BIS) has been recommended as a non invasive, practical, and relatively non expensive method to determine hydration and nutritional status in patients on maintenance hemodialysis (HD). In the current study we used whole body BIS analysis for determination of body water (BW) compartments; total body water (TBW), extracellular water (ECW), and intracellular water (ICW) in 133 healthy adults, and in 227 hemodialysis patients with end-stage renal disease. BIS results were compared to anthropometric measurements. Our results showed strong correlation between TBW measured by BIS in control group in comparison to anthropometric calculation (p = 0.001). In HD patients we observed higher range of TBW, and TBW/ECW ratio (from 15.6 to 56.1 L and from 0.33 to 0.78), as measured by BIS at pre-HD, and also post-HD period (TBW ranged from 13.1 to 56.2 L, ECW/TBW ratio ranged from 0.33 to 1.27). The TBW BIS results did not correlate with anthropometric calculation. We postulate using of multi-frequency bioimpedance technique in precise determination of fluid compartments and in consequence in the assessment of "target weight" in hemodialysis population.

  16. Tracking Target and Spiral Waves

    DEFF Research Database (Denmark)

    Jensen, Flemming G.; Sporring, Jon; Nielsen, Mads

    2002-01-01

    A new algorithm for analyzing the evolution of patterns of spiral and target waves in large aspect ratio chemical systems is introduced. The algorithm does not depend on finding the spiral tip but locates the center of the pattern by a new concept, called the spiral focus, which is defined...... by the evolutes of the actual spiral or target wave. With the use of Gaussian smoothing, a robust method is developed that permits the identification of targets and spirals foci independently of the wave profile. Examples of an analysis of long image sequences from experiments with the Belousov...

  17. Comparative Study on Theoretical and Machine Learning Methods for Acquiring Compressed Liquid Densities of 1,1,1,2,3,3,3-Heptafluoropropane (R227ea via Song and Mason Equation, Support Vector Machine, and Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Hao Li

    2016-01-01

    Full Text Available 1,1,1,2,3,3,3-Heptafluoropropane (R227ea is a good refrigerant that reduces greenhouse effects and ozone depletion. In practical applications, we usually have to know the compressed liquid densities at different temperatures and pressures. However, the measurement requires a series of complex apparatus and operations, wasting too much manpower and resources. To solve these problems, here, Song and Mason equation, support vector machine (SVM, and artificial neural networks (ANNs were used to develop theoretical and machine learning models, respectively, in order to predict the compressed liquid densities of R227ea with only the inputs of temperatures and pressures. Results show that compared with the Song and Mason equation, appropriate machine learning models trained with precise experimental samples have better predicted results, with lower root mean square errors (RMSEs (e.g., the RMSE of the SVM trained with data provided by Fedele et al. [1] is 0.11, while the RMSE of the Song and Mason equation is 196.26. Compared to advanced conventional measurements, knowledge-based machine learning models are proved to be more time-saving and user-friendly.

  18. Targeted intraoperative radiotherapy in oncology

    CERN Document Server

    Keshtgar, Mohammed; Wenz, Frederik

    2014-01-01

    Targeted intraoperative radiotherapy is a major advance in the management of cancer patients. With an emphasis on practical aspects, this book offers an ideal introduction to this innovative  technology for clinicians.

  19. Hyperspectral-Augmented Target Tracking

    National Research Council Canada - National Science Library

    Soliman, Neil A

    2008-01-01

    ... air with the capability to seek, monitor, and destroy mobile terrorist targets in hostile territory. One such capability recognizes and persistently tracks multiple moving vehicles in complex, highly ambiguous urban environments...

  20. After treat-to-target

    DEFF Research Database (Denmark)

    Wakefield, Richard J; D'Agostino, Maria Antonietta; Naredo, Esperanza

    2012-01-01

    have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted...... defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found...... in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who...

  1. After treat-to-target

    DEFF Research Database (Denmark)

    Wakefield, Richard J; D'Agostino, Maria Antonietta; Naredo, Esperanza

    2012-01-01

    have recently formed a research network--the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted...... defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found...... in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who...

  2. Targeted therapy for pediatric glioma

    NARCIS (Netherlands)

    Olow, A.K.

    2015-01-01

    This thesis assesses molecular underpinnings of responses to promising targeted agents for pediatric tumors of Central Nervous System (CNS), incorporating preclinical testing of novel and translatable combination therapies to define the best therapy for each tumor cell specific molecular aberration.

  3. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  4. National Ignition Facility Target Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Wavrik, R W; Cox, J R; Fleming, P J

    2000-10-05

    On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This

  5. Theoretical aspects of inflation targeting

    Directory of Open Access Journals (Sweden)

    Obradović Jelena

    2014-01-01

    Full Text Available Inflation targeting is one of the possible strategies used by central banks during conducting monetary policy. The basic characteristics, advantages and disadvantages of inflation targeting will be presented in this paper. The focus is on the the presentation and interpretation of the understanding of this strategy from the perspective of monetarist and Keynesian theory, the theory of rational expectations, and methodological analysis of the strategy in light of the game theory using payoff matrix.

  6. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  7. Targeting the nuclear RNA exosome

    DEFF Research Database (Denmark)

    Meola, Nicola; Jensen, Torben Heick

    2017-01-01

    Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is guided to its RNA targets by adaptor proteins that enable substrate recognition. Recently, the discovery of the 'Poly(A) tail exosome...... targeting (PAXT)' connection as an exosome adaptor to human nuclear polyadenylated transcripts has relighted the interest of poly(A) binding proteins (PABPs) in both RNA productive and destructive processes....

  8. Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs.

    Science.gov (United States)

    Venkova, Larisa; Aliper, Alexander; Suntsova, Maria; Kholodenko, Roman; Shepelin, Denis; Borisov, Nicolas; Malakhova, Galina; Vasilov, Raif; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-09-29

    Effective choice of anticancer drugs is important problem of modern medicine. We developed a method termed OncoFinder for the analysis of new type of biomarkers reflecting activation of intracellular signaling and metabolic molecular pathways. These biomarkers may be linked with the sensitivity to anticancer drugs. In this study, we compared the experimental data obtained in our laboratory and in the Genomics of Drug Sensitivity in Cancer (GDS) project for testing response to anticancer drugs and transcriptomes of various human cell lines. The microarray-based profiling of transcriptomes was performed for the cell lines before the addition of drugs to the medium, and experimental growth inhibition curves were built for each drug, featuring characteristic IC50 values. We assayed here four target drugs - Pazopanib, Sorafenib, Sunitinib and Temsirolimus, and 238 different cell lines, of which 11 were profiled in our laboratory and 227 - in GDS project. Using the OncoFinder-processed transcriptomic data on ~600 molecular pathways, we identified pathways showing significant correlation between pathway activation strength (PAS) and IC50 values for these drugs. Correlations reflect relationships between response to drug and pathway activation features. We intersected the results and found molecular pathways significantly correlated in both our assay and GDS project. For most of these pathways, we generated molecular models of their interaction with known molecular target(s) of the respective drugs. For the first time, our study uncovered mechanisms underlying cancer cell response to drugs at the high-throughput molecular interactomic level.

  9. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

    2003-01-01

    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...... autonomous star tracker the Advanced Stellar Compass (ASC). One feature of this instrument is that potential targets are registered directly in terms of date, right ascension, declination, and intensity, which greatly facilitates both tracking search and registering. Results from ground and inflight tests...

  10. Pharmacogenomics of GPCR Drug Targets

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

    2017-01-01

    Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

  11. INFLATION TARGETING IN EASTERN EUROPE

    Directory of Open Access Journals (Sweden)

    Laurian Lungu

    2006-05-01

    Full Text Available This paper addresses the inflation targeting approach in three transition economies, namely Hungary, Poland and the Czech Republic with the use of Taylor rules as benchmarks. The three economies considered have been successful at achieving disinflation, but deviations of inflation from its target have been persistent in all cases. Except for the Czech Republic, deviations from the Taylor rule are large and persistent, with Hungary displaying the largest fluctuations. Polish interest rates have consistently exceeded those suggested by the Taylor rule and given the prevalence of high unemployment, these undershootings do not augur well for the stability of monetary policy. Finally, the behaviour of Czech interest rates can be remarkably captured by the simple Taylor rule proposed in this paper, suggesting that the Czech National Bank has been the most successful at stabilising inflation and output around their target levels.

  12. Targeting Angiogenesis in Childhood Sarcomas

    Directory of Open Access Journals (Sweden)

    Hemant K. Bid

    2011-01-01

    Full Text Available Angiogenesis and vasculogenesis constitute two processes in the formation of new blood vessels and are essential for progression of solid tumors. Consequently, targeting angiogenesis, and to a lesser extent vasculogenesis, has become a major focus in cancer drug development. Angiogenesis inhibitors are now being tested in pediatric populations whereas inhibitors of vasculogenesis are in an earlier stage of development. Despite the initial enthusiasm for targeting angiogenesis for treatment of cancer, clinical trials have shown only incremental increases in survival, and agents have been largely cytostatic rather than inducing tumor regressions. Consequently, the role of such therapeutic approaches in the context of curative intent for childhood sarcomas is less clear. Here we review the literature on blood vessel formation in sarcomas with a focus on pediatric sarcomas and developments in targeting angiogenesis for treatment of these rare cancers.

  13. Ribosome Assembly as Antimicrobial Target

    Directory of Open Access Journals (Sweden)

    Rainer Nikolay

    2016-05-01

    Full Text Available Many antibiotics target the ribosome and interfere with its translation cycle. Since translation is the source of all cellular proteins including ribosomal proteins, protein synthesis and ribosome assembly are interdependent. As a consequence, the activity of translation inhibitors might indirectly cause defective ribosome assembly. Due to the difficulty in distinguishing between direct and indirect effects, and because assembly is probably a target in its own right, concepts are needed to identify small molecules that directly inhibit ribosome assembly. Here, we summarize the basic facts of ribosome targeting antibiotics. Furthermore, we present an in vivo screening strategy that focuses on ribosome assembly by a direct fluorescence based read-out that aims to identify and characterize small molecules acting as primary assembly inhibitors.

  14. Progress with developing a target for magnetized target fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wysocki, F.J.; Chrien, R.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T.

    1997-09-01

    Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. The goal of these experiments is to demonstrate plasma conditions meeting the minimum requirements for a MTF initial target plasma. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Thus far, the diagnostics include an array of 12 B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, filtered silicon photodiodes, neutron yield, and plasma-density interferometer. These diagnostics show that a plasma is produced in the containment region that lasts roughly 10 to 20 {micro}s with a maximum plasma density exceeding 10{sup 18} cm{sup {minus}3}. The experimental design and data are presented.

  15. Targeted Therapies for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Idoroenyi Amanam

    2018-01-01

    Full Text Available Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

  16. Harnessing off-target effects

    DEFF Research Database (Denmark)

    Saginc, Gaye; Voellmy, Franziska; Linding, Rune

    2017-01-01

    The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.......The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action....

  17. The OPERA experiment Target Tracker

    CERN Document Server

    Adam, T; Borer, K.; Campagne, Jean-Eric; Con-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schutz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Walchli, T.; Wilquet, G.; Wurtz, J.

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  18. Target-Centric Network Modeling

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.; Clark, Dr. Robert M.

    In Target-Centric Network Modeling: Case Studies in Analyzing Complex Intelligence Issues, authors Robert Clark and William Mitchell take an entirely new approach to teaching intelligence analysis. Unlike any other book on the market, it offers case study scenarios using actual intelligence......, and collaborative sharing in the process of creating a high-quality, actionable intelligence product. The case studies reflect the complexity of twenty-first century intelligence issues by dealing with multi-layered target networks that cut across political, economic, social, technological, and military issues....... Working through these cases, students will learn to manage and evaluate realistic intelligence accounts....

  19. TARGET Imbalances at Record Levels

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    TARGET is the payments system for making settlements between euro area economies and five other EU economies. Cross-border transactions generate claims/surpluses and liabilities/deficits among national central banks which “net out” for the system as a whole. These imbalances are manageable in rel...

  20. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  1. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    very often have to communicate to rather heterogeneous target groups that have little more in common than a certain geographical habitat. That goes against most schoolbook teaching in the field of communication, but is none the less the terms with which that kind of communication has to live...

  2. Emerging targets in treating pain.

    Science.gov (United States)

    Chang, David S; Raghavan, Rahul; Christiansen, Sandy; Cohen, Steven P

    2015-08-01

    To provide an overview on drug targets and emerging pharmacological treatment options for chronic pain. Chronic pain poses an enormous socioeconomic burden for the more than 30% of people who suffer from it, costing over $600 billion per year in the USA. In recent years, there has been a surge in preclinical and clinical research endeavors to try to stem this epidemic. Preclinical studies have identified a wide array of potential targets, with some of the most promising translational research being performed on novel opioid receptors, cannabinoid receptors, selective ion channel blockers, cytokine inhibitors, nerve growth factor inhibitors, N-methyl-D-aspartate receptor antagonists, glial cell inhibitors, and bisphosphonates. There are many obstacles for the development of effective medications to treat chronic pain, including the inherent challenges in identifying pathophysiological mechanisms, the overlap and multiplicity of pain pathways, and off-target adverse effects stemming from the ubiquity of drug target receptor sites and the lack of highly selective receptor ligands. Despite these barriers, the number and diversity of potential therapies have continued to grow, to include disease-modifying and individualized drug treatments.

  3. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  4. How are inflation targets set?

    Czech Academy of Sciences Publication Activity Database

    Horváth, R.; Matějů, Jakub

    -, č. 426 (2010), s. 1-35 ISSN 1211-3298 Grant - others:MŠk(CZ) SVV-2010-261801 Institutional research plan: CEZ:MSM0021620846 Keywords : inflation targeting * central bank * credibility Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp426.pdf

  5. High power neutron production targets

    Energy Technology Data Exchange (ETDEWEB)

    Wender, S. [Los Alamos National Lab., NM (United States)

    1996-06-01

    The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

  6. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could ...

  7. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  8. The Automatic Measurement of Targets

    DEFF Research Database (Denmark)

    Höhle, Joachim

    1997-01-01

    The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range...

  9. Polarized Scintillating Targets at Psi

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2001-02-01

    Scintillating polarized targets are now routinely available: blocks of 18×18×5 mm scintillating organic polymer, doped with TEMPO, polarized dynamically in a field of 2.5 T in a vertical 3He-4He dilution refrigerator. A 19 mm diameter plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat.

  10. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  11. Targeted Advertising and Social Status

    NARCIS (Netherlands)

    N. Vikander (Nick)

    2010-01-01

    textabstractThis paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties

  12. Polarimetric imaging of underwater targets

    Science.gov (United States)

    Gilerson, Alex; Carrizo, Carlos; Tonizzo, Alberto; Ibrahim, Amir; El-Habashi, Ahmed; Foster, Robert; Ahmed, Samir

    2013-06-01

    Underwater imaging is challenging because of the significant attenuation of light due to absorption and scattering of light in water. Using polarization properties of light is one of the options for improving image quality. We present results of imaging of a polarized target in open ocean (Curacao) and coastal (NY Bight) waters. The target in the shape of a square is divided into several smaller squares, each of which is covered with a polarizing film with different polarization orientations or transmission coefficients was placed on a mirror and imaged under water by a green-band full-Stokes polarimetric video camera at the full range of azimuth angles against the Sun. The values of the Stokes vector components from the images are compared with the modeled image of the target using radiative transfer code for the atmosphere-ocean system combined with the simple imaging model. It is shown that even in clear water the impact of the water body on the polarized underwater image is very significant and retrieval of target polarization characteristics from the image is extremely challenging.

  13. Target selection for direct marketing.

    NARCIS (Netherlands)

    Bult, Jan Roelf

    1993-01-01

    In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

  14. Uranium briquettes for irradiation target

    Energy Technology Data Exchange (ETDEWEB)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo, E-mail: saliba@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce {sup 99}Mo-{sup 99m}Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl{sub x} dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of {sup 235}U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  15. Collisional disruptions of rotating targets

    Science.gov (United States)

    Ševeček, Pavel; Broz, Miroslav

    2017-10-01

    Collisions are key processes in the evolution of the Main Asteroid Belt and impact events - i.e. target fragmentation and gravitational reaccumulation - are commonly studied by numerical simulations, namely by SPH and N-body methods. In our work, we extend the previous studies by assuming rotating targets and we study the dependence of resulting size-distributions on the pre-impact rotation of the target. To obtain stable initial conditions, it is also necessary to include the self-gravity already in the fragmentation phase which was previously neglected.To tackle this problem, we developed an SPH code, accelerated by SSE/AVX instruction sets and parallelized. The code solves the standard set of hydrodynamic equations, using the Tillotson equation of state, von Mises criterion for plastic yielding and scalar Grady-Kipp model for fragmentation. We further modified the velocity gradient by a correction tensor (Schäfer et al. 2007) to ensure a first-order conservation of the total angular momentum. As the intact target is a spherical body, its gravity can be approximated by a potential of a homogeneous sphere, making it easy to set up initial conditions. This is however infeasible for later stages of the disruption; to this point, we included the Barnes-Hut algorithm to compute the gravitational accelerations, using a multipole expansion of distant particles up to hexadecapole order.We tested the code carefully, comparing the results to our previous computations obtained with the SPH5 code (Benz and Asphaug 1994). Finally, we ran a set of simulations and we discuss the difference between the synthetic families created by rotating and static targets.

  16. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

  17. North Pacific Targets Program Environmental Assessment

    National Research Council Canada - National Science Library

    2001-01-01

    .... The STPO would provide the Strategic Target System launch vehicle for strategic target launch services from Kodiak Launch Complex, Kodiak Island, Alaska, a commercial rocket launch facility operated...

  18. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

    Science.gov (United States)

    Yang, Hu

    2016-02-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Emerging targets in human lymphoma: targeting the MYD88 mutation

    Directory of Open Access Journals (Sweden)

    Wang JQ

    2013-08-01

    Full Text Available James Q Wang,* Yogesh S Jeelall,* Keisuke Horikawa* Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia *All authors contributed equally to this manuscript Abstract: B cell neoplasms co-opt the molecular machinery of normal B cells for their survival. Technological advances in cancer genomics has significantly contributed to uncovering the root cause of aggressive lymphomas, revealing a previously unknown link between TLR signaling and B cell neoplasm. Recurrent oncogenic mutations in MYD88 have been found in 39% of the activated B cell-like subtype of diffuse large B cell lymphoma (ABC DLBCL. Interestingly, 29% of ABC DLBCL have a single amino acid substitution of proline for the leucine at position 265 (L265P, and the exact same variant has also been identified in a number of lymphoid malignancies. The MYD88 L265P variant was recently identified in 90% of Wadenstrom's macroglobulinemia patients. These recent developments warrant the need for novel diagnostic tools as well as targeted therapeutics. In this review, we discuss the physiological functions of MYD88 and focus on its role in B cell lymphomas, evaluating the potential for targeting oncogenic MYD88 in lymphoma. Keywords: MYD88, L265P mutation, lymphoma, targeted therapy

  20. Measurement of pretzelosity asymmetry of charged pion production in Semi-Inclusive Deep Inelastic Scattering on a polarized $^3$He target

    CERN Document Server

    Zhang, Y; Allada, K; Dutta, C; Huang, J; Katich, J; Wang, Y; Aniol, K; Annand, J R M; Averett, T; Benmokhtar, F; Bertozzi, W; Bradshaw, P C; Bosted, P; Camsonne, A; Canan, M; Cates, G D; Chen, C; Chen, J -P; Chen, W; Chirapatpimol, K; Chudakov, E; Cisbani, E; Cornejo, J C; Cusanno, F; Dalton, M M; Deconinck, W; de Jager, C W; De Leo, R; Deng, X; Deur, A; Ding, H; Dolph, P A M; Dutta, D; Fassi, L El; Frullani, S; Gao, H; Garibaldi, F; Gaskell, D; Gilad, S; Gilman, R; Glamazdin, O; Golge, S; Guo, L; Hamilton, D; Hansen, O; Higinbotham, D W; Holmstrom, T; Huang, M; Ibrahim, H F; Iodice, M; Jiang, X; Jin, G; Jones, M K; Kelleher, A; Kim, W; Kolarkar, A; Korsch, W; LeRose, J J; Li, X; Li, Y; Lindgren, R; Liyanage, N; Long, E; Lu, H -J; Margaziotis, D J; Markowitz, P; Marrone, S; McNulty, D; Meziani, Z -E; Michaels, R; Moffit, B; Camacho, C Muñoz; Nanda, S; Narayan, A; Nelyubin, V; Norum, B; Oh, Y; Osipenko, M; Parno, D; Peng, J C; Phillips, S K; Posik, M; Puckett, A J R; Qiang, Y; Rakhman, A; Ransome, R D; Riordan, S; Saha, A; Sawatzky, B; Schulte, E; Shahinyan, A; Shabestari, M H; Sirca, S; Stepanyan, S; Subedi, R; Sulkosky, V; Tang, L -G; Tobias, W A; Urciuoli, G M; Vilardi, I; Wang, K; Wojtsekhowski, B; Yan, X; Yao, H; Ye, Y; Ye, Z; Yuan, L; Zhan, X; Zhang, Y -W; Zhao, B; Zheng, X; Zhu, L; Zhu, X; Zong, X

    2013-01-01

    An experiment to measure single-spin asymmetries in semi-inclusive production of charged pions in deep-inelastic scattering on a transversely polarized $^3$He target was performed at Jefferson Lab in the kinematic region of $0.162<2.7$ ${\\rm GeV^2}$. The pretzelosity asymmetries on $^3$He, which can be expressed as the convolution of the $h^\\perp_{1T}$ transverse momentum dependent distribution functions and the Collins fragmentation functions in the leading order, were measured for the first time. Using the effective polarization approximation, we extracted the corresponding neutron asymmetries from the measured $^3$He asymmetries and cross-section ratios between the proton and $^3$He. Our results show that for both $\\pi^{\\pm}$ on $^3$He and on the neutron the pretzelosity asymmetries are consistent with zero within experimental uncertainties.

  1. Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides.

    Science.gov (United States)

    Sun, Jiawei; Jiang, Lei; Lin, Yi; Gerhard, Ethan Michael; Jiang, Xuehua; Li, Li; Yang, Jian; Gu, Zhongwei

    2017-01-01

    Mitochondria serve as both "energy factories" and "suicide weapon stores" of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips). Compared with Taxol (free PTX), RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50) value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs). An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6%) and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage tumor-targeting liposomes represent a promising anticancer drug delivery system (DDS) capable of maximizing anticancer therapeutic efficacy and minimizing systemic toxicity.

  2. Targeting an efficient target-to-target interval for P300 speller brain–computer interfaces

    Science.gov (United States)

    Sellers, Eric W.; Wang, Xingyu

    2013-01-01

    Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain–computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

  3. Newer targeted therapies in psoriasis

    Directory of Open Access Journals (Sweden)

    Sujay Khandpur

    2013-01-01

    Full Text Available Psoriasis is a common, chronic, inflammatory skin disease that can have a significant impact on the quality of life of those who are afflicted due to chronicity of the disease and frequent remissions and relapses. Many available systemic therapies, however, are unsuitable for chronic administration due to the risk of cumulative toxicity. Recent advances in the understanding of the pathophysiology of psoriasis have led to the development of new, genetically engineered, targeted therapies for this disease. These include approaches targeting antigen presentation and co-stimulation, T-cell activation and leukocyte adhesion, action on pro-inflammatory mediators, and modulating the cytokine balance. Although only preliminary data are available so far and there is limited data supporting their use, these trials contribute to a further understanding of the disease and will eventually lead to new therapeutic options for psoriasis.

  4. Moulding calixarenes for biomacromolecule targeting.

    Science.gov (United States)

    Giuliani, Marta; Morbioli, Ilaria; Sansone, Francesco; Casnati, Alessandro

    2015-09-28

    After their successful use as a preorganized platform for the preparation of receptors for metal ions and small neutral molecules over the last 15 years, calixarenes are enjoying a renaissance of popularity as scaffolds for ligands that are able to efficiently and selectively target macromolecules such as proteins/enzymes, nucleic acids and lipids. This feature article summarizes the peculiar factors characterizing the calixarene structure and properties, as well as outlines the main rules that can be used to turn such macrocycles into efficient and successful ligands for these classes of biomacromolecules. Factors that affect the multivalent properties of calixarenes, such as the size, conformation and stereochemical presentation of binding groups or their amphiphilicity and hybrid character, are described in detail with the use of a few selected examples from the literature. Perspectives and applications of these ligands in bionanotechnology and nanomedicine, such as protein sensing and inhibition, gene-delivery, targeted drug-delivery and cell imaging, are also discussed.

  5. Swimbladder on Fish Target Strength

    Directory of Open Access Journals (Sweden)

    Sunardi

    2008-08-01

    Full Text Available This paper discusses of target strength (TS for the Selar boops (Oxeye scad and Megalaspis cordyla (Torpedo scad, the most commercially fish in Malaysia. TS can be determined from in situ measurements and acoustic calculation of fish model. TS value, depth, and position (x-y-z of targeted fish can be viewed from echogram using FQ-80 Analyzer by in situ measurement. X-ray imaged can be deployed to develop the acoustic fish model. The percentage of length and upper surface area for swimbladder to body fish of Selar boops more than Megalaspis cordyla can be measured after X-ray process. The percentage of width and volume of swimbladders to its each body are no significantly difference for both fish. These data of swimbladder physic support the result of in situ measurement which TS of Megalaspis cordyla stronger Selar boops.

  6. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark

    2014-05-01

    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  7. Remote moving target indication assessment

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1996-10-01

    The objective of this project was to design and test key components of a sensor to be used on remotely piloted vehicles, aircraft, or satellites for the detection of moving vehicles in cluttered backgrounds. The proposed sensor uses modern large-array focal planes to provide multiple infrared observations of moving targets and capable on-board computers to integrate multiple observations to detect moving targets in background clutter. This combination reduces the size, weight, and cost of the sensor to levels that can be flown on many small unmanned platforms. This effort selected the actual components, integrated them into a test bed, tested the performance of the sensor against realistic generated scenes, and designed a proof-of-concept prototype.

  8. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...... are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug...... delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  9. Poverty, inequality, and geographic targeting

    OpenAIRE

    Simler, Kenneth R.; Nhate, Virgulino

    2005-01-01

    "This paper applies small area estimation techniques to Mozambican data to develop high resolution (subdistrictlevel) poverty and inequality maps...The picture that emerges is one of considerable local-level economic heterogeneity, with the poor living alongside the nonpoor. Rather than finding stark pockets of intense poverty traps in one part of the country and a relative absence of poverty in other parts, the situation is much more nuanced. This suggests that targeting antipoverty efforts ...

  10. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  11. Medium size polarised deuteron target

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, Yu.F.; Polyakov, V.V.; Kovalev, A.I.; Bunyatova, E.I.; Borisov, N.S.; Trautman, V.Yu.; Werner, K.; Kozlenko, N.G.

    1984-03-01

    A frozen polarised deuteron target based on ethanediol with a high percentage of deuterium is described. Analytical expressions for the NMR spectrum correction for non-linearity of the Q-meter are obtained and a method for the determination of the asymmetry is developed. Experimental results confirm the thermal mixing theory for deuteron and proton spin systems with a dipole-dipole reservoir of electron spins.

  12. Peptide-targeted polymer cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S153-S164 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * tumor targeting * peptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S153.pdf

  13. Coherent Communications, Imaging and Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Stappaerts, E; Baker, K; Gavel, D; Wilks, S; Olivier, S; Brase, J; Olivier, S; Brase, J

    2003-10-03

    Laboratory and field demonstration results obtained as part of the DARPA-sponsored Coherent Communications, Imaging and Targeting (CCIT) program are reviewed. The CCIT concept uses a Phase Conjugation Engine based on a quadrature receiver array, a hologram processor and a spatial light modulator (SLM) for high-speed, digital beam control. Progress on the enabling MEMS SLM, being developed by a consortium consisting of LLNL, academic institutions and small businesses, is presented.

  14. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    What opportunities for training and professional development has the project provided? Two graduate students and one postdoctoral research associate...hostile immune reaction toward FR-expressing tumors. A series of vaccinations with hapten fluorescein (EC90 vaccine ) admin- istrated with an adjuvant...FITC-conjugated (FITC is flu - orescein isothiocyanate) CA inhibitor acetalozamide (AAZ) targeted CA-IX positive cells (Kd = 12.6 nM). The biodistribution

  15. Targeting inflammation in metabolic syndrome.

    Science.gov (United States)

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Targeting distress in rheumatic diseases

    OpenAIRE

    Vriezekolk, J.E.

    2011-01-01

    Psychological distress is highly prevalent in patients with rheumatic diseases. It is associated with a variety of negative outcomes, including pain, fatigue, disability, and maladaptive cognitive behavioural coping strategies. In this thesis, psychological distress was studied both as an outcome measure and as a therapeutic target in the context of multidisciplinary rehabilitation. The longitudinal role of coping in psychological distress was systematically reviewed, a questionnaire to asses...

  17. Novel therapies targeting vascular endothelium.

    Science.gov (United States)

    Tousoulis, Dimitris; Antoniades, Charalambos; Koumallos, Nikolaos; Marinou, Kyriakoula; Stefanadi, Elli; Latsios, George; Stefanadis, Christodoulos

    2006-01-01

    Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature may improve the long-term outcome in healthy individuals, high-risk subjects, or patients with advanced atherosclerosis. Several therapeutic strategies are now available, targeting both the synthesis and oxidative inactivation of nitric oxide (NO) in human vasculature. Statins seem to be currently the most powerful category of these agents, improving endothelial function and decreasing cardiovascular risk after long-term administration. Other cardiovascular agents improving endothelial function in humans are angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, which increase NO bioavailability by modifying the rennin-angiotensin-aldosterone system. Newer therapeutic approaches targeting endothelial dysfunction in specific disease states include insulin sensitizers, L-arginine (the substrate for endothelial NO synthase [eNOS]) as well as substances that target eNOS "coupling," such as folates or tetrahydrobiopterin. Although there are a variety of strategies to improve NO bioavailability in human endothelium, it is still unclear whether they have any direct benefit at a clinical level.

  18. Targeted gene flow for conservation.

    Science.gov (United States)

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

  19. Targeted Treatment Options in Mastocytosis

    Directory of Open Access Journals (Sweden)

    Mélanie Vaes

    2017-07-01

    Full Text Available Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM or in various organs (systemic mastocytosis, SM. This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia. In addition, SM may be associated with hematological neoplasms (AHN. While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN. Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy.

  20. Unmanned Aircraft Systems (UAS) Sensor and Targeting

    Science.gov (United States)

    2010-07-27

    mission, a pre-determined number of different targets should be shuffled between the target locations in the array. Example targets for this subtest are...UNFOV Ultra Narrow Field of View UTM Universal Transverse Mercator VBLSS Video-Based Laser Scoring System VRT Vertical Reference Target WFOV

  1. Progress with developing a target for magnetized target fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wysocki, F.J.; Chrien, B.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T. [Los Alamos National Lab., NM (United States)

    1997-12-31

    Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Follow-on experiments will use a frozen deuterium fiber along the axis (without a gas-fill). The diagnostics include B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, silicon photodiodes, neutron yield, and plasma-density interferometer. Operation to date has been with drive current ranging from 0.8 MA to 1.9 MA. Optical diagnostics show that the plasma produced in the containment region lasts roughly 20 to 30 {micro}s, and the B-dot probes show a broad current-profile in the containment region. The experimental design and data will be presented.

  2. Targeted advertising, platform competition and privacy

    OpenAIRE

    Henk Kox; Bas Straathof; Gijsbert Zwart

    2014-01-01

    Targeted advertising can benefit consumers through lower prices for access to websites. Yet, if consumers dislike that websites collect their personal information, their welfare may go down. We study competition for consumers between websites that can show targeted advertisements. We find that more targeting increases competition and reduces the websites' profits, but yet in equilibrium websites choose maximum targeting as they cannot credibly commit to low targeting. A privacy protection pol...

  3. Triatoma dimidiata infestation in Chagas disease endemic regions of Guatemala: comparison of random and targeted cross-sectional surveys.

    Directory of Open Access Journals (Sweden)

    Raymond J King

    Full Text Available BACKGROUND: Guatemala is presently engaged in the Central America Initiative to interrupt Chagas disease transmission by reducing intradomiciliary prevalence of Triatoma dimidiata, using targeted cross-sectional surveys to direct control measures to villages exceeding the 5% control threshold. The use of targeted surveys to guide disease control programs has not been evaluated. Here, we compare the findings from the targeted surveys to concurrent random cross-sectional surveys in two primary foci of Chagas disease transmission in central and southeastern Guatemala. METHODOLOGY/PRINCIPAL FINDINGS: Survey prevalences of T. dimidiata intradomiciliary infestation by village and region were compared. Univariate logistic regression was used to assess the use of risk factors to target surveys and to evaluate indicators associated with village level intradomiciliary prevalences >5% by survey and region. Multivariate logistic regression models were developed to assess the ability of random and targeted surveys to target villages with intradomiciliary prevalence exceeding the control threshold within each region. Regional prevalences did not vary by survey; however, village prevalences were significantly greater in random surveys in central (13.0% versus 8.7% and southeastern (22.7% versus 6.9% Guatemala. The number of significant risk factors detected did not vary by survey in central Guatemala but differed considerably in the southeast with a greater number of significant risk factors in the random survey (e.g. land surface temperature, relative humidity, cropland, grassland, tile flooring, and stick and mud and palm and straw walls. Differences in the direction of risk factor associations were observed between regions in both survey types. The overall discriminative capacity was significantly greater in the random surveys in central and southeastern Guatemala, with an area under the receiver-operator curve (AUC of 0.84 in the random surveys and

  4. Hospitals: Soft Target for Terrorism?

    Science.gov (United States)

    De Cauwer, Harald; Somville, Francis; Sabbe, Marc; Mortelmans, Luc J

    2017-02-01

    In recent years, the world has been rocked repeatedly by terrorist attacks. Arguably, the most remarkable were: the series of four coordinated suicide plane attacks on September 11, 2001 on buildings in New York, Virginia, and Pennsylvania, USA; and the recent series of two coordinated attacks in Brussels (Belgium), on March 22, 2016, involving two bombings at the departure hall of Brussels International Airport and a bombing at Maalbeek Metro Station located near the European Commission headquarters in the center of Brussels. This statement paper deals with different aspects of hospital policy and disaster response planning that interface with terrorism. Research shows that the availability of necessary equipment and facilities (eg, personal protective clothing, decontamination rooms, antidotes, and anti-viral drugs) in hospitals clearly is insufficient. Emergency teams are insufficiently prepared: adequate and repetitive training remain necessary. Unfortunately, there are many examples of health care workers and physicians or hospitals being targeted in both political or religious conflicts and wars. Many health workers were kidnapped and/or killed by insurgents of various ideology. Attacks on hospitals also could cause long-term effects: hospital units could be unavailable for a long time and replacing staff could take several months, further compounding hospital operations. Both physical and psychological (eg, posttraumatic stress disorder [PTSD]) after-effects of a terrorist attack can be detrimental to health care services. On the other hand, physicians and other hospital employees have shown to be involved in terrorism. As data show that some offenders had a previous history with the location of the terror incident, the possibility of hospitals or other health care services being targeted by insiders is discussed. The purpose of this report was to consider how past terrorist incidents can inform current hospital preparedness and disaster response planning

  5. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  6. Downstream targets of WRKY33

    DEFF Research Database (Denmark)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John

    2008-01-01

    Innate immunity signaling pathways in both animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. In a recent publication we show that MPK4 and its substrate MKS1 interact with WRKY33 in vivo, and that WRKY33 is released from complexes with MPK4 upon infection. Tran...... immunoprecipitation confirmed that WRKY33 bound the promoter of PAD3 when plants were inoculated with pathogens. Here we further discuss the involvement of two other targets of WRKY33, NUDT6 and ROF2 in defense responses against invading pathogens....

  7. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...... of the ‘inside’ costs of the sub-component, technical specifications of the product, opportunistic behavior from the suppliers and cognitive limitation. These are all aspects that easily can dismantle the market mechanism and make it counter-productive in the organization. Thus, by directing more attention...

  8. The challenge of targeting metastasis.

    Science.gov (United States)

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

    Metastases that are resistant to conventional therapy are the major cause of death from cancer. In most patients, metastasis has already occurred by the time of diagnosis. Thus, the prevention of metastasis is unlikely to be of therapeutic benefit. The biological heterogeneity of metastases presents a major obstacle to treatment. However, the growth and survival of metastases depend on interactions between tumor cells and host homeostatic mechanisms. Targeting these interactions, in addition to the tumor cells, can produce synergistic therapeutic effects against existing metastases.

  9. Introduction to radar target recognition

    CERN Document Server

    Tait, P

    2006-01-01

    This new text provides an overview of the radar target recognition process and covers the key techniques being developed for operational systems. It is based on the fundamental scientific principles of high resolution radar, and explains how the techniques can be used in real systems, taking into account the characteristics of practical radar system designs and component limitations. It also addresses operational aspects, such as how high resolution modes would fit in with other functions such as detection and tracking. Mathematics is kept to a minimum and the complex techniques and issues are

  10. Targeting α-synuclein oligomers

    DEFF Research Database (Denmark)

    van Diggelen, Femke

    2017-01-01

    Parkinson’s Disease (PD) is a complex disease, characterised by degeneration of neocortical, limbic and nigrostriatal neurons. It is unknown what initiates neurodegeneration, but soluble oligomers of the protein α-synuclein (αSn) seem to be particularly toxic, compared to insoluble fibrils....... Although there is currently no cure for PD, αSn oligomers (αSOs) are a potential therapeutic target, but a major drawback it that little is known about the nature of PD-associated αSOs. The scientific literature describes a wide variety of protocols to generate αSOs in vitro, with a subsequent...

  11. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  12. Targeting telomerase with radiolabeled inhibitors.

    Science.gov (United States)

    Waghorn, Philip A; Jackson, Mark R; Gouverneur, Veronique; Vallis, Katherine A

    2017-01-05

    The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123 I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123 I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC 50 of 1.58 μM (MST-312 IC 50 : 0.23 μM). Clonogenic assays showed a dose dependant effect of 123 I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  13. Properties of Protein Drug Target Classes

    Science.gov (United States)

    Bull, Simon C.; Doig, Andrew J.

    2015-01-01

    Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID

  14. Bioengineering Strategies for Designing Targeted Cancer Therapies

    Science.gov (United States)

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  15. TARGET 2 and Settlement Finality

    Directory of Open Access Journals (Sweden)

    Ivan MANGATCHEV

    2011-03-01

    Full Text Available This article examines how TARGET 2 as system implements the idea of settlement finality regulated by Directive 98/26 EC of the European parliament and of the Council of 19 May 1998 on settlement finality in payment and securities settlement systems (Settlement Finality Directive and Directive 2009/44/EC of the European parliament and of the Council of 6 May 2009 amending Directive 98/26/EC on settlement finality in payment and securities settlement systems and Directive 2002/47/EC on financial collateral arrangements as regards linked systems and credit claims (Directive 2009/44/EC. As the title of the arti and finality of the settlement in this system.

  16. Terahertz-based target typing.

    Energy Technology Data Exchange (ETDEWEB)

    Lyo, Sungkwun Kenneth; Wanke, Michael Clement; Reno, John Louis; Shaner, Eric Arthur; Grine, Albert D.; Barrick, Todd A.

    2008-09-01

    The purpose of this work was to create a THz component set and understanding to aid in the rapid analysis of transient events. This includes the development of fast, tunable, THz detectors, along with filter components for use with standard detectors and accompanying models to simulate detonation signatures. The signature effort was crucial in order to know the spectral range to target for detection. Our approach for frequency agile detection was to utilize plasmons in the channel of a specially designed field-effect transistor called the grating-gate detector. Grating-gate detectors exhibit narrow-linewidth, broad spectral tunability through application of a gate bias, and no angular dependence in their photoresponse. As such, if suitable sensitivity can be attained, they are viable candidates for Terahertz multi-spectral focal plane arrays.

  17. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  18. Targeting Persistent Human Papillomavirus Infection.

    Science.gov (United States)

    Shanmugasundaram, Srinidhi; You, Jianxin

    2017-08-18

    While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.

  19. Targeting ECM Disrupts Cancer Progression

    DEFF Research Database (Denmark)

    Venning, Freja A; Wullkopf, Lena; Erler, Janine T

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the ex...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.......Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings......, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...

  20. Obesity treatment: novel peripheral targets.

    Science.gov (United States)

    Field, Benjamin C T; Chaudhri, Owais B; Bloom, Stephen R

    2009-12-01

    Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short- and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies.

  1. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  2. Target therapies in pancreatic carcinoma.

    Science.gov (United States)

    Silvestris, Nicola; Gnoni, Antonio; Brunetti, Anna Elisabetta; Vincenti, Leonardo; Santini, Daniele; Tonini, Giuseppe; Merchionne, Francesca; Maiello, Evaristo; Lorusso, Vito; Nardulli, Patrizia; Azzariti, Amalia; Reni, Michele

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments.

  3. Combinatorial microRNA target predictions

    DEFF Research Database (Denmark)

    Krek, Azra; Grün, Dominic; Poy, Matthew N.

    2005-01-01

    MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed...... in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published micro......RNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results...

  4. Targets and processes for fabricating same

    Science.gov (United States)

    Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

    2014-06-10

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  5. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  6. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

    NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

  7. On the large COMPASS polarized deuteron target

    CERN Document Server

    Finger, M; Baum, G; Doshita, N; Finger, M Jr; Gautheron, F; Goertz, St; Hasegawa, T; Heckmann, J; Hess, Ch; Horikawa, N; Ishimoto, S; Iwata, T; Kisselev, Y; Koivuniemi, J; Kondo, K; Le Goff, J-M; Magnon, A; Marchand, C; Matsuda, T; Meyer, W; Reicherz, G; Srnka, A

    2006-01-01

    The spin structure of the nucleons is investigated in deep inelastic scattering of a polarized muon beam and a polarized nucleon target in the COMPASS experiment at CERN since 2001. To achieve high luminosities a large solid polarized target is used. The COMPASS polarized target consists of a high cooling power $^{3}$He/$^{4}$He dilution refrigerator capable to maintain working temperature of the target material at about 50mK, a superconducting solenoid and dipole magnet system for longitudinal and transversal magnetic field on the target material, respectively, target cells containing polarizable material, microwave cavities and high power microwave radiation systems for dynamic nuclear polarization and the nuclear magnetic resonance system for nuclear spin polarization measurements. During 2001–2004 experiments superconducting magnet system with opening angle $\\pm$69 mrad, polarized target holder with two target cells and corresponding microwave and NMR systems have been used. For the data taking from 200...

  8. Targeting Cancer with Antisense Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes

  9. Production of neutron-rich nuclides in the heavy-element region via /sup 3/He-induced reactions

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Y.Y.; Zhou, M.L.

    1982-01-01

    We have measured the production cross sections for /sup 233/Th and /sup 231/Th from the bombardment of /sup 238/U with /sup 3/He ions at 46-, 53-, and 60-MeV at the Brookhaven 60-in. isochronous cyclotron. We have also attempted to observe the decay of /sup 233/Ac produced via /sup 238/U(/sup 3/He,/sup 8/B) or equivalent reactions using 61 MeV /sup 3/He ions by first separating thorium from actinium and then performing chemical purifications on the second thorium sample into which the actinium has decayed. In the four experiments we performed, three gave results consistent with the ..beta.. half-life of /sup 233/Ac somewhat longer than 120 s and the production cross section from this target-projectile combination in the order of 1 to 2 ..mu..b.

  10. Targeted integration of genes in Xenopus tropicalis

    DEFF Research Database (Denmark)

    Shi, Zhaoying; Tian, Dandan; Xin, Huhu

    2017-01-01

    With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous...... recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis....

  11. Capacitive Sensors And Targets Would Measure Alignments

    Science.gov (United States)

    Jenstrom, Del T.

    1994-01-01

    Multiple capacitive sensors and active targets used to measure distance between, and relative orientation of, two objects. Sensed target signals processed and used by control systems to align objects to be joined. Shapes, sizes, and layouts of sensors and targets optimized for specific application. Particular layout of targets and sensors enables determination of relative position and orientation of two objects in all six degrees of freedom.

  12. 40 CFR 35.9020 - Planning targets.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Planning targets. 35.9020 Section 35... STATE AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant Administrator for Water develops planning targets each year to help each...

  13. Inflation Targeting and Business Cycle Synchronization

    OpenAIRE

    Flood, Robert P; Rose, Andrew K

    2009-01-01

    Inflation targeting seems to have a small but positive effect on the synchronization of business cycles; countries that target inflation seem to have cycles that move slightly more closely with foreign cycles. Thus the advent of inflation targeting does not explain the decoupling of global business cycles, for two reasons. Indeed business cycles have not in fact become less synchronized across countries.

  14. Starkweather Target Game for Preschool Children.

    Science.gov (United States)

    Starkweather, Elizabeth K.

    The Starkweather Target Game is designed to measure preschool children's willingness to try difficult tasks independent of ability. The game consists of a box-shaped target which responds, when the target is hit by a rolled ball, somewhat like a jack-in-a-box. When the bull's eye is hit, the lid opens and a surprise picture appears. After being…

  15. Vergence facility with stereoscopic and nonstereoscopic targets.

    Science.gov (United States)

    Momeni-Moghaddam, Hamed; Goss, David A; Dehvari, Abubakr

    2014-05-01

    To compare vergence facility with nonstereo and stereo targets in binocular symptomatic and asymptomatic subjects. Sixty-six students were divided into symptomatic and asymptomatic groups according to the Convergence Insufficiency Symptom Survey Questionnaire score. Vergence facility was tested at 40 cm by flipper prism 3Δ BI/12Δ BO (BI, base-in; BO, base-out). The targets used were a nonstereo target (a vertical column of small letter "E" of ~20/30 size), a stereo-local target (fifth set of circles of the Titmus test with stereoacuity of 100 arcsec), and a stereo-global target (page 6 of the TNO test with stereoacuity of 120 arcsec). Repeated-measures analysis of variance showed differences in the mean vergence facility with different targets in all subjects and separately in two symptom groups (p 0.05) but significant for the comparison of stereo-global targets with the other two targets. The receiver operating characteristic curve analysis showed the cutoff points 10.5, 10.5, and 9.75 cycles per minute with nonstereo, stereo-local, and stereo-global targets, respectively. The sensitivity of the three targets used was the same (97%). Specificity was 0.93 or higher with all three targets, with the highest specificity obtained with the stereo-global target (100%). The highest vergence facility was obtained with a nonstereo target and the lowest was obtained with a stereo-global target. High sensitivity with all three targets means that there are few false-negative results with them, and the high specificity is indicative of low false-positive results. Hence, the vergence facility predictive value would be high in diagnosing binocular symptomatic patients using a 3Δ BI/12Δ BO prism flipper at near and a response cutoff of about 10 cycles per minute or less.

  16. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  17. Tantalum/Copper X-Ray Targets

    Science.gov (United States)

    Waters, William J.; Edmonds, Brian

    1993-01-01

    Lewis Research Center developed unique solution to subsidiary problem of fabrication of x-ray target. Plasma spraying enabled fabrication of lightweight, high-performance targets. Power settings, atmosphere-control settings, rate of deposition, and other spraying parameters developed. Thin coats of tantalum successfully deposited on copper targets. Targets performed successfully in tests and satisfied all criteria expressed in terms of critical parameters. Significantly reduces projected costs of fabrication of targets and contributes to development of improved, long-lived, lightweight x-ray system.

  18. Targeting nominal income growth or inflation?

    DEFF Research Database (Denmark)

    Jensen, Henrik

    2002-01-01

    Within a simple New Keynesian model emphasizing forward-looking behavior of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy is mainly subject to shocks that do not involve monetary policy trade-offs for society, inflation...... targeting is preferable. Otherwise, nominal income growth targeting may be superior because it induces inertial policy making, which improves the inflation-output-gap trade-off. Somewhat paradoxically, inflation targeting may be relatively less favorable the more society dislikes inflation, and the more...

  19. Improved Targeting of Cancers with Nanotherapeutics

    DEFF Research Database (Denmark)

    Foster, Christian; Watson, Andre; Kaplinsky, Joseph John

    2017-01-01

    Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting...... ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along...... with recent developments for cancer-targeted nanomedicines....

  20. Graphite target for the spiral project

    Energy Technology Data Exchange (ETDEWEB)

    Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire; Bertrand, P. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Loiselet, M. [Universite Catholique de Louvain, Louvain-La-Neuve (Belgium)] [and others

    1996-12-31

    A study of the thermal and physical properties of graphite targets for the SPIRAL project is presented. The main objective is to develop an optimized set-up both mechanically and thermally resistant, presenting good release properties (hot targets with thin slices). The results of irradiation tests concerning the mechanical and thermal resistance of the first prototype of SPIRAL target with conical geometry are presented. The micro-structural properties of the graphite target is also studied, in order to check that the release properties are not deteriorated by the irradiation. Finally, the results concerning the latest pilot target internally heated by an electrical current are shown. (author). 5 refs.

  1. The trajectory of the target probability effect.

    Science.gov (United States)

    Hon, Nicholas; Yap, Melvin J; Jabar, Syaheed B

    2013-05-01

    The effect of target probability on detection times is well-established: Even when detection accuracy is high, lower probability targets are detected more slowly than higher probability ones. Although this target probability effect on detection times has been well-studied, one aspect of it has remained largely unexamined: How the effect develops over the span of an experiment. Here, we investigated this issue with two detection experiments that assessed different target probability ratios. Conventional block segment analysis and linear mixed-effects modeling converged on two key findings. First, we found that the magnitude of the target probability effect increases as one progresses through a block of trials. Second, we found, by examining the trajectories of the low- and high-probability targets, that this increase in effect magnitude was driven by the low-probability targets. Specifically, we found that low-probability targets were detected more slowly as a block of trials progressed. Performance to high-probability targets, on the other hand, was largely invariant across the block. The latter finding is of particular interest because it cannot be reconciled with accounts that propose that the target probability effect is driven by the high-probability targets.

  2. Secondary anchor targeted cell release.

    Science.gov (United States)

    Ansari, Ali; Lee-Montiel, Felipe T; Amos, Jennifer R; Imoukhuede, P I

    2015-11-01

    Personalized medicine offers the promise of tailoring therapy to patients, based on their cellular biomarkers. To achieve this goal, cellular profiling systems are needed that can quickly and efficiently isolate specific cell types without disrupting cellular biomarkers. Here we describe the development of a unique platform that facilitates gentle cell capture via a secondary, surface-anchoring moiety, and cell release. The cellular capture system consists of a glass surface functionalized with APTES, d-desthiobiotin, and streptavidin. Biotinylated mCD11b and hIgG antibodies are used to capture mouse macrophages (RAW 264.7) and human breast cancer (MCF7-GFP) cell lines, respectively. The surface functionalization is optimized by altering assay components, such as streptavidin, d-desthiobiotin, and APTES, to achieve cell capture on 80% of the functionalized surface and cell release upon biotin treatment. We also demonstrate an ability to capture 50% of target cells within a dual-cell mixture. This engineering advancement is a critical step towards achieving cell isolation platforms for personalized medicine. © 2015 Wiley Periodicals, Inc.

  3. Targeting ceramide metabolism in obesity.

    Science.gov (United States)

    Aburasayn, Hanin; Al Batran, Rami; Ussher, John R

    2016-08-01

    Obesity is a major health concern that increases the risk for insulin resistance, type 2 diabetes (T2D), and cardiovascular disease. Thus, an enormous research effort has been invested into understanding how obesity-associated dyslipidemia and obesity-induced alterations in lipid metabolism increase the risk for these diseases. Accordingly, it has been proposed that the accumulation of lipid metabolites in organs such as the liver, skeletal muscle, and heart is critical to these obesity-induced pathologies. Ceramide is one such lipid metabolite that accumulates in tissues in response to obesity, and both pharmacological and genetic strategies that reduce tissue ceramide levels yield salutary actions on overall metabolic health. We will review herein why ceramide accumulates in tissues during obesity and how an increase in intracellular ceramide impacts cellular signaling and function as well as potential mechanisms by which reducing intracellular ceramide levels improves insulin resistance, T2D, atherosclerosis, and heart failure. Because a reduction in skeletal muscle ceramide levels is frequently associated with improvements in insulin sensitivity in humans, the beneficial findings reported for reducing ceramides in preclinical studies may have clinical application in humans. Therefore, modulating ceramide metabolism may be a novel, exciting target for preventing and/or treating obesity-related diseases. Copyright © 2016 the American Physiological Society.

  4. Resource implications of a national health target

    DEFF Research Database (Denmark)

    Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

    2014-01-01

    Background The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. Method A survey...... of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped...... into categories: structure (facilities/beds), staff and processes. Simple statistics were used to describe the data, and the correlation between expenditure and target performance was determined. Results There was 100% response to the survey. Most DHBs reported some expenditure specifically on the target...

  5. Targeting dendritic cells--why bother?

    Science.gov (United States)

    Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

    2013-04-11

    Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

  6. Preliminary study of mercury target structure

    Energy Technology Data Exchange (ETDEWEB)

    Kaminaga, Masanori; Haga, Katsuhiro; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Kumasaka, Katsuyuki; Uchida, Shoji; Nakagawa, Toshi; Mori, Seiji; Nishikawa, Akira

    1997-11-01

    Development of a proton accelerator based neutron source (1.5 GeV, 5.3 mA (for neutron source 3.3 mA), thermal power 8 MW) is currently conducted by the Special Task Force for Neutron Science Initiative, JAERI. Preliminary design studies and related R and D of a solid metal target for the first stage (1.5 GeV, 1 mA) and a liquid metal target for both the first and second stages (1.5 GeV, 3.3 mA) are conducted by the Target Group to develop both solid and liquid metal target systems. A few kinds of target structures have been investigated in FY 1996 and the preliminary results for the target structures are described in this paper. Investigation results of alternative materials for the target container are also described in this paper. (author)

  7. Governing by targets : Reductio ad unum and evolution of the two-degree climate target

    NARCIS (Netherlands)

    Morseletto, Piero; Biermann, Frank|info:eu-repo/dai/nl/176991662; Pattberg, Philipp

    2017-01-01

    Targets are widely employed in environmental governance. In this paper, we investigate the construction of the 2 °C climate target, one of the best known targets in global environmental governance. Our paper examines this target through a historical reconstruction that identifies four different

  8. Using the Dual-Target Cost to Explore the Nature of Search Target Representations

    Science.gov (United States)

    Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2012-01-01

    Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

  9. Target definition for shipwreck hunting

    Directory of Open Access Journals (Sweden)

    Kim Paul Kirsner

    2015-10-01

    Full Text Available The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or ‘mean’ just 2.7 NM (nautical miles from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor’s reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013. The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  10. Target definition for shipwreck hunting.

    Science.gov (United States)

    Kirsner, Kim

    2015-01-01

    The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or "mean" just 2.7 NM (nautical miles) from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor's reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013). The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  11. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  12. Target detection and tracking in infrared video

    Science.gov (United States)

    Deng, Zhihui; Zhu, Jihong

    2017-07-01

    In this paper, we propose a method for target detection and tracking in infrared video. The target is defined by its location and extent in a single frame. In the initialization process, we use an adaptive threshold to segment the target and then extract the fern feature and normalize it as a template. The detector uses the random forest and fern to detect the target in the infrared video. The random forest and fern is a random combination of 2bit Binary Pattern, which is robust to infrared targets with blurred and unknown contours. The tracker uses the gray-value weighted mean-Shift algorithm to track the infrared target which is always brighter than the background. And the tracker can track the deformed target efficiently and quickly. When the target disappears, the detector will redetect the target in the coming infrared image. Finally, we verify the algorithm on the real-time infrared target detection and tracking platform. The result shows that our algorithm performs better than TLD in terms of recall and runtime in infrared video.

  13. [Influenza telephone consultation target the general public--2003-2004, 2004-2005].

    Science.gov (United States)

    Yamadera, Shizuko; Kobune, Fumio; Komatsu, Toshihiko; Suzuki, Kazuyoshi; Nakayama, Mikio; Hagiwara, Toshikatsu; Matsumoto, Miyako; Yamamoto, Kiichi; Renard, Junko; Oya, Akira

    2007-07-01

    The NPO Biomedical Science Association provided telephone consultation, including contacts by fax and email, targeting the general public within the framework of influenza control measures worked out by the Japanese Ministry of Health, Labor and Welfare (MHLW). We received 2,813 inquiries during the 2003-2004 flu season and 2,444 inquiries during the 2004-2005 season. By month, the highest number was in October-November, accounting for 42.6%. The preceding season showed a similar trend. By gender, 72.5% of those seeking advice were women. By area of residence, the highest number was living in metropolitan Tokyo, and the remainder lived in the prefectures of Kanagawa, Chiba, Saitama, Nagano, Shizuoka, and Ibaraki in this order. We received no inquiries from the prefectures of Shimane or Saga. By occupation, housewives accounted for 1,114 inquiries (45.6%), followed by private companies with 447 inquiries (18.3%) and health-care providers with 227 inquiries (9.3%), similar to the 2003-2004 flu season. By subject, 1,545 inquiries concerned vaccines (62.2%) mainly, the pros and cons of vaccination, adverse reactions, and the number of inoculations required. Inquiries about pregnancy, infants and young children, and breast-feeding accounted for 19.2%. Inquiries on vaccine shortages during the 2004-2005 flu season (7), SARS (22), and bird flu (22) decreased compared to the previous season, while the number of consultations on antiviral agents increased (209). In discussing how information on influenza should be communicated to the public, we propose that "Influenza Q & A" provided by the Infectious Diseases Surveillance Center of the NIID, MHLW, should include information on influenza specifically addressing pregnant woman and breast-feeding or child-rearing mothers.

  14. Fluid mechanics aspects of magnetic drug targeting.

    Science.gov (United States)

    Odenbach, Stefan

    2015-10-01

    Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.

  15. Resistance to Antibiotics Mediated by Target Alterations

    Science.gov (United States)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  16. High power target developments at ISAC

    CERN Document Server

    Bricault, P G; Dowling, A; Lane, M

    2003-01-01

    TRIUMF, Canada's national research facility for particle and nuclear physics is currently operating the ISAC facility. A high-energy proton beam from the H sup - TRIUMF cyclotron is used to generate short-lived radioactive species in a thick target. An ion source at the target creates a radioactive beam, which is then injected into the ISAC beam lines and accelerator system. The ISAC facility is designed to accept proton beam intensity up to 100 mu A at 500 MeV. At present our target design can only sustains 40 mu A at maximum. Beyond this point the target has to be cooled. A new target equipped with fins has been developed that may sustain proton beam up to 100 mu A. The fined target has been tested off-line and a thermal simulation using ANSYS[reg] has been conducted and the results are reported here.

  17. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano; David, Jean-Christophe; Leray, Sylvie; Letourneau, Alain; Michel-Sendis, Franco; Stankunas, Gediminas [CEA/IRFU, Gif-sur-Yvette (France); Berg, Klara; Filges, Uwe; Groeschel, Friedrich; Luethy, Markus; Scazzi, Selene; Tobler, Leonhard; Zanini, Luca [PSI, Villigen (Switzerland); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Gif-sur-Yvette (France); Guertin, Arnaud; Thiolliere, Nicolas [SUBATECH, Nantes (France); Konobeyev, Alexander Yu. [FZK/IRS, Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, St. Paul Lez Durance (France); Lemaire, Sebastien [CEA/DAM/DCSA/SCGA, Bruyeres-le-Chatel (France)

    2008-07-01

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). The project is an important step in the road-map towards the demonstration of the Accelerator Driven System (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment. (authors)

  18. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France)], E-mail: Stefano.panebianco@cea.fr; Berg, Klara [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); David, Jean-Christophe [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Centre de Saclay, F-91194 Gif-sur-Yvette (France); Filges, Uwe; Groeschel, Friedrich [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Guertin, Arnaud [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Konobeyev, Alexander Yu [Forschungszentrum Karlsruhe, IRS, D-76021 Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, Centre de Cadarache, F-13108 Saint-Paul-lez-Durance (France); Lemaire, Sebastien [CEA, DAM Ile de France, F-91297 Bruyeres le Chatel (France); Leray, Sylvie; Letourneau, Alain [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Luethy, Markus [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Michel-Sendis, Franco [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Scazzi, Selene [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Stankunas, Gediminas [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Thiolliere, Nicolas [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Tobler, Leonhard; Zanini, Luca [Paul Scherrer Institut, CH-5232 Villigen (Switzerland)

    2009-04-15

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of about 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). This project is an important step in the roadmap towards the demonstration of the accelerator driven system (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment.

  19. Polarized targets in high energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Cates, G.D. Jr. [Princeton Univ., NJ (United States)

    1994-12-01

    Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, an experiment to measure the spin structure function of the neutron, and is described in detail.

  20. THERMAL OSCILLATIONS IN LIQUID HELIUM TARGETS.

    Energy Technology Data Exchange (ETDEWEB)

    WANG,L.; JIA,L.X.

    2001-07-16

    A liquid helium target for the high-energy physics was built and installed in the proton beam line at the Alternate Gradient Synchrotron of Brookhaven National Laboratory in 2001. The target flask has a liquid volume of 8.25 liters and is made of thin Mylar film. A G-M/J-T cryocooler of five-watts at 4.2K was used to produce liquid helium and refrigerate the target. A thermosyphon circuit for the target was connected to the J-T circuit by a liquid/gas separator. Because of the large heat load to the target and its long transfer lines, thermal oscillations were observed during the system tests. To eliminate the oscillation, a series of tests and analyses were carried out. This paper describes the phenomena and provides the understanding of the thermal oscillations in the target system.

  1. Protection Related to High-power Targets

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Target protection is an important part of machine protection. The beam power in high-intensity accelerators is high enough that a single wayward pulse can cause serious damage. Today's high-power targets operate at the limit of available technology, and are designed for a very narrow range of beam parameters. If the beam pulse is too far off centre, or if the beam size is not correct, or if the beam density is too high, the target can be seriously damaged. We will start with a brief introduction to high-power targets and then move to a discussion of what can go wrong, and what are the risks. Next we will discuss how to control the beam-related risk, followed by examples from a few different accelerator facilities. We will finish with a detailed example of the Oak Ridge Spallation Neutron Source target tune up and target protection.

  2. Visualizing Energy on Target: Molecular Dynamics Simulations

    Science.gov (United States)

    2017-12-01

    ARL-TR-8234 ● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics Simulations by DeCarlos E...return it to the originator. ARL-TR-8234● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics...REPORT TYPE Technical Report 3. DATES COVERED (From - To) 1 October 2015–30 September 2016 4. TITLE AND SUBTITLE Visualizing Energy on Target

  3. ENTERPRISE RESOURCE STRATEGIC PLANNING: TARGET CHOICE TECHNIQUES

    Directory of Open Access Journals (Sweden)

    A. S. Lankin

    2011-01-01

    Full Text Available Choice of the targets is one of most important elements of the resource planning system. Particular feature of the strategic planning is development of future alternatives for the enterprise. Main resource strategic planning cycle elements: examination of principal external and internal environment components; forming the company mission; development of long-term targets; concretization of the long-term targets through short-term aims; examination of strategies and final choice.

  4. Targeting Malignant Brain Tumors with Antibodies

    OpenAIRE

    Rok Razpotnik; Neža Novak; Vladka Čurin Šerbec; Uros Rajcevic

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain deli...

  5. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...... and co-targets for single-epitope and multi-epitope strategies. We provide examples of application to the well-known tumor antigen HER2 and suggest bioinformatics methods to ameliorate therapy resistance and ensure efficient and lasting control of tumors....

  6. Promoting target models by potential measures

    OpenAIRE

    Dubiel, Joerg

    2010-01-01

    Direct marketers use target models in order to minimize the spreading loss of sales efforts. The application of target models has become more widespread with the increasing range of sales efforts. Target models are relevant for offline marketers sending printed mails as well as for online marketers who have to avoid intensity. However business has retained its evaluation since the late 1960s. Marketing decision-makers still prefer managerial performance measures of the economic benefit of a t...

  7. Design of the LBNF Beamline Target Station

    OpenAIRE

    Tariq, S.; Ammigan, K.; Anderson, K.; Buccellato, S. A.; Crowley, C. F.; Hartsell, B. D.; Hurh, P.; Hylen, J.; Kasper, P.; Krafczyk, G. E.; Lee, A.; Lundberg, B.; Marchionni, A; Mokhov, N. V.; Moore, C. D.

    2016-01-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-fil...

  8. Target R and D at JAERI

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)

  9. Target Language Adaptation of Discriminative Transfer Parsers

    OpenAIRE

    Täckström, Oscar; McDonald, Ryan; Nivre, Joakim

    2013-01-01

    We study multi-source transfer parsing for resource-poor target languages; specifically methods for target language adaptation of delexicalized discriminative graph-based dependency parsers. We first show how recent insights on selective parameter sharing, based on typological and language-family features, can be applied to a discriminative parser by carefully decomposing its model features. We then show how the parser can be relexicalized and adapted using unlabeled target language data and ...

  10. Magnetic confinement system using charged ammonia targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1979-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  11. COST OF ADDRESSING TARGETS OF UNEQUAL VALUE

    Energy Technology Data Exchange (ETDEWEB)

    G.H. CANAVAN

    2001-08-01

    The formalism for evaluating first strike costs and incentives for military targeting generalize to include higher value targets. That introduces two new allocations to the usual allocation between missiles and military targets, but they can be performed analytically. As the number of weapons on each side decreases, the optimal fraction of second strike weapons allocated to military values falls. The shift to high value targets is more pronounced below about 1,000 weapons for nominal parameters. Below 500 weapons the first striker's cost of action drops below its cost of inaction. A strike would induce a second strike of about 250 weapons on high value targets. An increase in the first striker's preference for damage to the other's high value targets increases or a decrease in its preference for preventing damage to its own high value targets decreases first strike costs and stability margins. Including defenses complicates allocations slightly. The main effect is increased attrition of second strikes, particularly at larger defenses, which makes it possible to significantly reduce damage to high value targets. At 1,000 weapons, by 300 to 400 interceptors the first striker's costs are reduced to 30% below that of inaction and the number of weapons delivered on the first striker's high value targets is reduced to about 100.

  12. What makes a good drug target?

    Science.gov (United States)

    Gashaw, Isabella; Ellinghaus, Peter; Sommer, Anette; Asadullah, Khusru

    2012-02-01

    Novel therapeutics in areas with a high unmet medical need are based on innovative drug targets. Although 'biologicals' have enlarged the space of druggable molecules, the number of appropriate drug targets is still limited. Discovering and assessing the potential therapeutic benefit of a drug target is based not only on experimental, mechanistic and pharmacological studies but also on a theoretical molecular druggability assessment, an early evaluation of potential side effects and considerations regarding opportunities for commercialization. This article defines key properties of a good drug target from the perspective of a pharmaceutical company. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Uncertainty Prediction in Passive Target Motion Analysis

    Science.gov (United States)

    2016-05-12

    denote the bearing and range from observer 12B to target 10B at time t2 as indicated in FIG. 3. Between times t1 and t2, observer 12A has traveled over...Cartesian coordinates of the target with respect to time , and ?̇? and ?̇? are components of the target velocity. [0007] As is well known, a...as a time interval of constant platform velocity.) [0008] In addition to a point estimate of the current target state, a representation of the

  14. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those...

  15. An entropy model with variable target

    OpenAIRE

    K O Jörnsten; Larsson, T; J T Lundgren; Migdalas, A.

    1990-01-01

    In this paper an entropy model with variable target is presented, in which target values are assumed to belong to a specified convex set, so that multiple base-year information and forecasts of future trends can be handled without prior aggregation of such information into one fixed target. Three solution methods for such a model are presented -- one cutting-plane and two search methods -- all of which utilize the fact that entropy models with fixed targets can be solved efficiently. Some com...

  16. Tumour-targeted nanomedicines: principles and practice

    National Research Council Canada - National Science Library

    Lammers, T.G.G.M; Hennink, W.E; Storm, G

    2008-01-01

    .... Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents...

  17. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  18. Two target localization using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2016-02-19

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localization and tracking purposes. Many works focused on accurately localizing one or two targets laying within a narrow beam centered around the monopulse antenna boresight direction. In this work, however, a new approach uses the outputs of a four quadrant antenna receiver to rapidly localize two point targets present in the hemisphere. A second set of antennas can be required to localize two targets sharing the same elevation or azimuth angles. To combine the outputs of both antenna sets and enhance the estimation performance of the algorithm, two methods are presented and compared.

  19. Targeted advertising, platform competition and privacy

    NARCIS (Netherlands)

    Kox, Henk; Straathof, Bas; Zwart, Gijsbert

    2017-01-01

    Targeted advertising can benefit consumers through lower prices for access to web sites. Yet, if consumers dislike that web sites collect their personal information, their welfare may go down. We study competition for consumers between web sites that can show targeted advertisements. We find that

  20. A rotating target for Ra production

    NARCIS (Netherlands)

    Sohani, M.; Wilschut, H. W.

    2012-01-01

    A target wheel with pyrolytic graphite targets is designed and constructed at the TRI mu P facility to boost the production rate of Ra isotopes. Simulation, design properties and production results are discussed. (C) 2012 Elsevier B.V. All rights reserved.

  1. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Galambos, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Anderson, David E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bechtol, D. [HDR, Inc., Chattanooga, TN (United States); Bethea, Katie L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, N. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Carden, W. F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chae, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clark, A. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Counce, Deborah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Craft, K. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Crofford, Mark T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Collins, Richard M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cousineau, Sarah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Curry, Douglas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cutler, Roy I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dayton, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dean, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Deibele, Craig E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Doleans, Marc [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dye, T. [HDR, Inc., Chattanooga, TN (United States); Eason, Bob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eckroth, James A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fincrock, C. [HDR, Inc., Chattanooga, TN (United States); Fritts, S. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gawne, Ken R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hartman, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Herwig, Kenneth W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hess, S. [HDR, Inc., Chattanooga, TN (United States); Holmes, Jeffrey A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Horak, Charlie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howell, Matthew P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Iverson, Erik B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jacobs, Lorelei L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jones, Larry C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Johnson, B. [HDR, Inc., Chattanooga, TN (United States); Johnson, S. [HDR, Inc., Chattanooga, TN (United States); Kasemir, Kay [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kim, Sang-Ho [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Laughon, Gregory J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lu, W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mahoney, Kelly L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mammosser, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McManamy, T. [McManamy Consulting, Inc., Knoxville, TN (United States); Michilini, M. [HDR, Inc., Chattanooga, TN (United States); Middendorf, Mark E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); O' Neal, Ed [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nemec, B. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Peters, Roy Cecil [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Plum, Michael A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Reagan, G. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Remec, Igor [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Rennich, Mark J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Riemer, Bernie [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saethre, Robert B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Schubert, James Phillip [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shishlo, Andrei P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Smith, C. Craig [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strong, William Herb [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tallant, Kathie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tennant, David Alan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibadeau, Barbara M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Trumble, S. [HDR, Inc., Chattanooga, TN (United States); Trotter, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Z. [Institute of Modern Physics (IMP), Chinese Academy of Sciences (China); Webb, Steven B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Derrick C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); White, Karen S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhao, Jinkui [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    The Second Target Station (STS) is a proposed upgrade for SNS. It includes a doubling of the accelerator power and an additional instrument hall. The new instrument hall will receive a 467 kW 10 Hz beam. The parameters and preliminary design aspects of the STS are presented for the accelerator, target systems, instrument hall, instruments and civil construction aspects.

  2. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Green, Mark A.

    2000-03-22

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy.

  3. NIF Target Assembly Metrology Methodology and Results

    Energy Technology Data Exchange (ETDEWEB)

    Alger, E. T. [General Atomics, San Diego, CA (United States); Kroll, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dzenitis, E. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Montesanti, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hughes, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Swisher, M. [IAP, Livermore, CA (United States); Taylor, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Segraves, K. [IAP, Livermore, CA (United States); Lord, D. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Castro, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Edwards, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-01-01

    During our inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) we require cryogenic targets at the 1-cm scale to be fabricated, assembled, and metrologized to micron-level tolerances. During assembly of these ICF targets, there are physical dimensmetrology is completed using optical coordinate measurement machines that provide repeatable measurements with micron precision, while also allowing in-process data collection for absolute accuracy in assembly. To date, 51 targets have been assembled and metrologized, and 34 targets have been successfully fielded on NIF relying on these metrology data. In the near future, ignition experiments on NIF will require tighter tolerances and more demanding target assembly and metrology capability. Metrology methods, calculations, and uncertainty estimates will be discussed. Target diagnostic port alignment, target position, and capsule location results will be reviewed for the 2009 Energetics Campaign. The information is presented via control charts showing the effect of process improvements that were made during target production. Certain parameters, including capsule position, met the 2009 campaign specifications but will have much tighter requirements in the future. Finally, in order to meet these new requirements assembly process changes and metrology capability upgrades will be necessary.

  4. Inflation targeting and interest rate policy

    NARCIS (Netherlands)

    Verhagen, W.H.

    2001-01-01

    The thesis contains a collection of papers on issues in inflation targeting and its implications for the way interest rates are set. In this respect, the first part deals with two largely positive issues: the effect of inflation forecast targeting on the term structure of interest rates and the

  5. Population ageing and public finance targets

    OpenAIRE

    Heikki Oksanen

    2003-01-01

    The paper incorporates intergenerational fairness into a framework to analyse long-term sustainability of public finances under population ageing. It establishes a link between ageing-related public expenditure projections and public finance targets, thereby clarifying the connection between pension reforms and general government budget balance and debt targets.

  6. Thin Scintillating Polarized Targets for Spin Physics

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.

    2003-07-01

    At PSI polarized scintillating targets are available since 1996. Proton polarizations of more than 80%, and deuteron polarizations of 25% in polystyrene-based scintillators can be reached under optimum conditions in a vertical dilution refrigerator with optical access, suited for nuclear and particle physics experiments. New preparation procedures allow to provide very thin polarizable scintillating targets and widen the spectrum of conceivable experiments.

  7. Harmonic Phase Response of Nonlinear Radar Targets

    Science.gov (United States)

    2015-10-01

    ARL-TR-7513 ● OCT 2015 US Army Research Laboratory Harmonic Phase Response of Nonlinear Radar Targets by Sean F McGowan, Dr...Laboratory Harmonic Phase Response of Nonlinear Radar Targets by Sean F McGowan and Kelly D Sherbondy Sensors and Electron Devices Directorate...

  8. Function and targets of Fusarium oxysporum effectors

    NARCIS (Netherlands)

    Gawehns, F.K.K.

    2014-01-01

    A multi-layered immune system protects plants against pathogens. Adapted pathogens overcome or evade this immune system by secreting small proteins, called effectors. Often susceptibility genes encode host targets for these effectors, and loss-of-function mutations in such target genes can confer

  9. Security analysts' target prices and takeover premiums

    NARCIS (Netherlands)

    Gerritsen, Dirk F.

    2015-01-01

    Most existing studies conclude that the accuracy of analysts' target prices is questionable. In forecasting target prices, analysts estimate a future stock price under the constraint of a time frame of usually 12. months. We exclude this source of uncertainty by focusing on valuations in takeover

  10. ISOLDE target zone control room HD

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  11. Poverty Targeting Classifications and Distributional Effects

    OpenAIRE

    Elio H Londero

    2004-01-01

    This paper reviews two common definitions of poverty targeted projects, discusses the limitations of poverty targeting classifications, calls for a poverty focused cost-benefit analysis that looks at the main policy constraints affecting the distribution of project benefits, and argues for looking at the distribution of net benefits. Finally, it offers some conclusions for the distributionally-minded applied economists.

  12. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  13. Experimental identification of microRNA targets

    DEFF Research Database (Denmark)

    Ørom, Ulf Andersson; Lund, Anders H

    2009-01-01

    microRNAs are small RNAs that regulate protein synthesis post-transcriptionally. Animal microRNAs recognize their targets by incomplete base pairing to sequence motifs most often present in the 3' untranslated region of their target mRNAs. This partial complementarity vastly expands the repertoire...

  14. Targeted toxins in brain tumor therapy.

    Science.gov (United States)

    Li, Yan Michael; Hall, Walter A

    2010-11-01

    Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

  15. Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

    Science.gov (United States)

    Brown, K; Gordon, E; Williams, L; Bahramali, H; Harris, A; Gray, J; Gonsalvez, C; Meares, R

    2000-11-01

    While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

  16. Setting conservation targets for sandy beach ecosystems

    Science.gov (United States)

    Harris, Linda; Nel, Ronel; Holness, Stephen; Sink, Kerry; Schoeman, David

    2014-10-01

    Representative and adequate reserve networks are key to conserving biodiversity. This begs the question, how much of which features need to be placed in protected areas? Setting specifically-derived conservation targets for most ecosystems is common practice; however, this has never been done for sandy beaches. The aims of this paper, therefore, are to propose a methodology for setting conservation targets for sandy beach ecosystems; and to pilot the proposed method using data describing biodiversity patterns and processes from microtidal beaches in South Africa. First, a classification scheme of valued features of beaches is constructed, including: biodiversity features; unique features; and important processes. Second, methodologies for setting targets for each feature under different data-availability scenarios are described. From this framework, targets are set for features characteristic of microtidal beaches in South Africa, as follows. 1) Targets for dune vegetation types were adopted from a previous assessment, and ranged 19-100%. 2) Targets for beach morphodynamic types (habitats) were set using species-area relationships (SARs). These SARs were derived from species richness data from 142 sampling events around the South African coast (extrapolated to total theoretical species richness estimates using previously-established species-accumulation curve relationships), plotted against the area of the beach (calculated from Google Earth imagery). The species-accumulation factor (z) was 0.22, suggesting a baseline habitat target of 27% is required to protect 75% of the species. This baseline target was modified by heuristic principles, based on habitat rarity and threat status, with final values ranging 27-40%. 3) Species targets were fixed at 20%, modified using heuristic principles based on endemism, threat status, and whether or not beaches play an important role in the species' life history, with targets ranging 20-100%. 4) Targets for processes and 5

  17. Radiochemical aspects of liquid mercury spallation targets

    CERN Document Server

    Neuhausen, Joerg; Eichler, Bernd; Eller, Martin; Horn, Susanne; Schumann, Dorothea; Stora, Thierry

    2012-01-01

    Liquid metal spallation targets using mercury as target material are used in state-of-the-art high power pulsed neutron sources that have been constructed in the USA and Japan within the last decade. Similar target concepts were also proposed for next generation ISOL, beta-beam and neutrino facilities. A large amount of radioactivity will be induced in the liquid metal during operation caused by the interaction of the target material with the intense proton beam. This radioactivity - carried by a wide range of radioisotopes of all the elements of the periodic table from hydrogen up to thallium - must be considered for the assessment of safe operation and maintenance procedures as well as for a final disposal of the used target material and components. This report presents an overview on chemical investigations performed in our laboratory that deal with the behavior of radionuclides in proton irradiated mercury samples. The solubility of elements in mercury was calculated using thermodynamical data obtained by...

  18. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

    2009-12-15

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  19. Hydrogen isotope recycling at a tungsten target

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, M., E-mail: sakamoto@prc.tsukuba.ac.jp [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Nakashima, Y. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Higashizono, Y. [Research Institute for Applied Mechanics, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Ogawa, K. [Interdisciplinary Graduate School for Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Hosoi, K. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Rusinov, A. [Interdisciplinary Graduate School for Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Takeda, H.; Akabane, Y.; Kohagura, J.; Yoshikawa, M.; Ichimura, M.; Imai, T. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan)

    2013-07-15

    Hydrogen recycling has been studied focusing on the neutral behavior in front of tungsten target in the plasma–wall interaction simulator APSEDAS and the tandem mirror GAMMA 10. The line intensity of hydrogen Balmer series decreased toward the target corresponding to a decrease in the electron density in APSEDAS. The relative population of n = 3 and n = 4 increased and that of n = 5 and n = 6 decreased just in front of the target (Z < 5 mm). This might be attributed to the reflected atom or reemitted molecule from the target. In GAMMA 10, the intensity of hydrogen Balmer (H{sub α}) line decreased exponentially with distance from the target with two decay lengths: ∼16 mm and ∼53 mm. These two short decay lengths are attributed to the fact that a fraction of the reflected atoms and atoms dissociated from molecules are at excited energy states.

  20. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  1. Delayed neutrons measurement at the MEGAPIE target

    CERN Document Server

    Panebianco, Stefano; Dore, Diane; Ledoux, Xavier; Letourneau, Alain; Prevost, Aurelien; Ridikas, Danas

    2007-01-01

    In the framework of the Neutronic and Nuclear Assessment Task Group of the MEGAPIE experiment we measured the delayed neutron (DN) flux at the top of the target. The measurement was proposed mainly for radioprotection purposes since the DN flux at the top of the target has been estimated to be of the same order of magnitude as the prompt neutron flux. Given the strong model-dependence of DN predictions, the measurement of DN contribution to the total neutron activity at the top of the target was thus desired. Moreover, this measurement is complementary to the DN experiments performed at PNPI (Gatchina) on solid lead and bismuth targets. The DN measurement at MEGAPIE was performed during the start-up phase of the target. In this paper we present a detailed description of the experimental setup and some preliminary results on decay spectra.

  2. Launch window definition for sky target experiments.

    Science.gov (United States)

    Michaud, N. H.

    1973-01-01

    This paper is a brief report on the computer program developed for the Extraterrestrial Physics Barium Ion Cloud (BIC) Project. The mathematical analysis developed for the program along with its programing characteristics are pointed out to show that this program is adaptable to similar sky target projects. Definite viewing constraints are specified so that the chosen ground tracking stations can photograph the behavior of the sky target after its release. Viewing factors include the illumination of the target by the sun, the relative elevation look angle to the target from each tracking station, the solar and lunar depression angles at each tracking station, and the total sky background brightness of the target relative to each tracking station. Numeric values are assigned to each factor through program input. The program output is flexible so that the results of the window calculations can be studied to the depth required.

  3. Target Identification Strategies in Plant Chemical Biology

    Directory of Open Access Journals (Sweden)

    Wim eDejonghe

    2014-07-01

    Full Text Available The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starter blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, while studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology

  4. Radar target identification using multifractal geometry

    Science.gov (United States)

    Quach, Ban; Leung, Henry; Lo, Titus K. Y.; Litva, John

    1996-06-01

    The design of a system to distinguish objects from measurements of their radar backscatter signals has been a topic of considerable investigation. In the identification of a particular target out of a library of possible targets, the difficulty is that the radar signals cannot be fed rawly into a classifier. Some signal processing has to be done to generate the signal features for target identification. In this paper, multifractal geometry is applied to address the practical issue of discrimination between fishing boat, growlers (small pieces of glacial ice) and sea scattered signals, which is important for search-and-rescue operation. An efficient box-counting method is used to compute the generalized dimension and the multifractal spectrum of different targets and sea scattered signals. In an effort to support our study, X-band radar measurements were collected and analyzed to determine the separability of sea surface targets and sea scattered signals using the multifractal geometry.

  5. The Jefferson Lab Frozen Spin Target

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Keith, James Brock, Christopher Carlin, Sara Comer, David Kashy, Josephine McAndrew, David Meekins, Eugene Pasyuk, Joshua Pierce, Mikell Seely

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  6. Peptide Selection for Targeted Protein Quantitation.

    Science.gov (United States)

    Chiva, Cristina; Sabidó, Eduard

    2017-03-03

    Targeted proteomics methods in their different flavors rely on the use of a few peptides as proxies for protein quantitation, which need to be specified either prior to or after data acquisition. However, in contrast with discovery methods that use all identified peptides for a given protein to estimate its abundance, targeted proteomics methods are limited in the number of peptides that are used for protein quantitation. Because only a few peptides per protein are acquired or extracted in targeted experiments, the selection of peptides that are used for targeted protein quantitation becomes crucial. Several rules have been proposed to guide peptide selection for targeted proteomics studies, which have generally been based on the amino acidic composition of the peptide sequences. However, the compliance of these rules does not imply that not-conformed peptides are not reproducibly generated nor do they guarantee that the selected peptides correctly represent the behavior of the protein abundance under different conditions.

  7. Behavioral and neurophysiological aspects of target interception.

    Science.gov (United States)

    Merchant, Hugo; Zarco, Wilbert; Prado, Luis; Pérez, Oswaldo

    2009-01-01

    This chapter focuses on the behavioral and neurophysiological aspects of manual interception. We review the most important elements of an interceptive action from the sensory and cognitive stage to the motor side of this behavior. We describe different spatial and temporal target parameters that can be used to control the interception movement, as well as the different strategies used by the subject to intercept a moving target. We review the neurophysiological properties of the parietofrontal system during target motion processing and during a particular experiment of target interception. Finally, we describe the neural responses associated with the temporal and spatial parameters of a moving target and the possible neurophysiological mechanisms used to integrate this information in order to trigger an interception movement.

  8. Ecosystem Targets - Defining target levels for ecosystem components: a socio-ecological approach

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecological indicators can facilitate Ecosystem-based Management, but only if targets for indicators exist. Because targets are an expression of the desired state of...

  9. Multiple Model Adaptive Estimator Target Tracker for Maneuvering Targets in Clutter

    National Research Council Canada - National Science Library

    Smith, Brian D

    2005-01-01

    ...) to be implemented directly. Poorly known or varying target dynamics complicate the design of any tracking filter, and filters using only a single dynamics model can rarely handle anything beyond the most benign target maneuvers...

  10. 48 CFR 227.7013 - Recordation.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Infringement Claims... Commissioner of Patents and Trademarks, for recording, all Government interests in patents or applications for...

  11. Publications | Page 227 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Managing International Labour Migration in ASEAN : final technical report (open access). The project drew from varied experiences of six (three sending and three receiving) countries in the Association of Southeast Nations (ASEAN), to cover migration management issues from the perspective of sending and receiving ...

  12. 49 CFR 227.5 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... second or less. Decibel (dB) means a unit of measurement of sound pressure levels. dB(A) means the sound pressure level in decibels measured on the A-weighted scale. Employee means any individual who is engaged... this part. Exchange rate means the change in sound level, in decibels, which would require halving or...

  13. 49 CFR 227.121 - Recordkeeping.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating... person's representative upon written authorization by such employee; (iii) Make exposure measurement... were present in the locomotive cab during the given run and/or who work in the same yard; and (iv) Make...

  14. 50 CFR 600.227 - Lobbying.

    Science.gov (United States)

    2010-10-01

    ... and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Commerce implementing regulations published at 15 CFR part 28, “New Restrictions on Lobbying.” These..., employees, and contractors must comply with the Federal Cost Principles Applicable to Regional Fishery...

  15. 47 CFR 1.227 - Consolidations.

    Science.gov (United States)

    2010-10-01

    ... application. (ii) Domestic public fixed and public mobile. See Rule § 21.31 of this chapter for the... as to amendments of applications. (iii) Public coast stations (Maritime mobile service). See... such action will best conduce to the proper dispatch of business and to the ends of justice...

  16. 40 CFR 227.18 - Factors considered.

    Science.gov (United States)

    2010-07-01

    ... characteristics of the material to be dumped, allowing for conservative rates of dilution, dispersion, and... persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence...

  17. QTL Information Table: 227 [Q-TARO

    Lifescience Database Archive (English)

    Full Text Available Pa-In, N., Vongsaprom, C., and Toojinda, T. (2002). Quantitative Trait Loci Associated with Leaf and Neck Blast Resistance in Recomb...inant Inbred Line Population of Rice (Oryza Sativa). DNA

  18. Reference: 227 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available AtGA3ox4 but not AtGA20ox3 also showed their signals at the rim of the developing embryo. The alpha-amylase ...gene, Amy3, which responded to gibberellin, was mainly expressed in the developing

  19. Publications | Page 227 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This dissertation sought to add to knowledge of the links between human and ecosystem health by examining relationships between biodiversity and human nutrition in the East Usambara Mountains, Tanzania. Grounded in a theoretical framework drawing from systems approaches to human and EcoHealth.

  20. 40 CFR 227.13 - Dredged materials.

    Science.gov (United States)

    2010-07-01

    ... material with particle sizes larger than silt, and the material is found in areas of high current or wave energy such as streams with large bed loads or coastal areas with shifting bars and channels; or (2... existing and historical sources of pollution so as to provide reasonable assurance that such material has...

  1. Publications | Page 227 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Through books, articles, research publications, and studies, we aim to widen the impact of our investment and advance development research. ... and Communication Technologies (ICTs) as well as innovation in how ICTs are leveraged to support social, cultural and economic development needs in the Asia Pacific region,.

  2. 22 CFR 227.105 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... the Federal Acquisition Regulation (FAR), and any other acquisition contract for real or personal... tribes in that Act. (h) Influencing or attempting to influence means making, with the intent to influence...

  3. BDML Metadata: 227 [SSBD[Archive

    Lifescience Database Archive (English)

    Full Text Available Ce_KK_P002 BDML file for quantitative information about nuclear division dynamics o...f T23G5.1(RNAi) embryo quantitative information about nuclear division dynamics in T23G5.1(RNAi) embryo (rnr...-1(RNAi) embryo) C. elegans nuclear division dynamics T23G5.1(gPCR)061102_01 Measurement Kyoda, K., Furukawa

  4. 7 CFR 227.40 - Program information.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... Carolina, and Tennessee: Southeast Regional Office, FNS, U.S. Department of Agriculture, 1100 Spring Street... Wisconsin: Midwest Regional Office, FNS, U.S. Department of Agriculture, 536 South Clark Street, Chicago...

  5. Danish Media coverage of 22/7

    DEFF Research Database (Denmark)

    Hervik, Peter; Boisen, Sophie

    2013-01-01

    ’s Danish connections through an analysis of the first 100 days of Danish media coverage. We scrutinised 188 articles in the largest daily newspapers to find out how Danish actors related to ABB’s ideas. The key argument is that the discourses and opinions reflect pre-existing opinions and entrenched...

  6. 49 CFR 227.119 - Training program.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad Operating... concerning the expected range of workplace noise exposure levels associated with major categories of railroad...

  7. Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

    Science.gov (United States)

    Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

    2012-01-01

    Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

  8. Hitting moving targets : A dissociation between the use of the target's speed and direction of motion

    NARCIS (Netherlands)

    Brouwer, Anne Marie; Middelburg, Tom; Smeets, Jeroen B J; Brenner, Eli

    2003-01-01

    Previous work has indicated that people do not use their judgment of a target's speed to determine where to hit it. Instead, they use their judgment of the target's changing position and an expected speed (based on the speed of previous targets). In the present study we investigate whether people

  9. In silico exploration of novel phytoligands against probable drug target of Clostridium tetani.

    Science.gov (United States)

    Skariyachan, Sinosh; Prakash, Nisha; Bharadwaj, Navya

    2012-12-01

    Though tetanus is an old disease with well known medicines, its complications are still a serious issue worldwide. Tetanus is mainly due to a powerful neurotoxin, tetanolysin-O, produced by a Gram positive anaerobic bacterium, Clostridium tetani. The toxin has a thiol-activated cytolysin which causes lysis of human platelets, lysosomes and a variety of subcellular membranes. The existing therapy seems to have challenged as available vaccines are not so effective and the bacteria developed resistance to many drugs. Computer aided approach is a novel platform to screen drug targets and design potential inhibitors. The three dimensional structure of the toxin is essential for structure based drug design. But the structure of tetanolysin-O is not available in its native form. Moreover, the interaction and pharmacological activities of current drugs against tetanolysin-O is not clear. Hence, there is need for three dimensional model of the toxin. The model was generated by homology modeling using crystal structure of perfringolysin-O, chain-A (PDB ID: 1PFO) as the template. The modeled structure has 22.7% α helices, 27.51% β sheets and 41.75% random coils. A thiol-activated cytolysin was predicted in the region of 105 to 1579, which acts as a functional domain of the toxin. The hypothetical model showed the backbone root mean square deviation (RMSD) value of 0.6 Å and the model was validated by ProCheck. The Ramachandran plot of the model accounts for 92.3% residues in the most allowed region. The model was further refined by various tools and deposited to Protein Model Database (PMDB ID: PM0077550). The model was used as the drug target and the interaction of various lead molecules with protein was studied by molecular docking. We have selected phytoligands based on literatures and pharmacophoric studies. The efficiency of herbal compounds and chemical leads was compared. Our study concluded that herbal derivatives such as berberine (7, 8, 13, 13a-tetradehydro-9

  10. Origin of elements of the Uranium-235 family observed in the Ellez river near the EL-4 experimental nuclear reactor in dismantling (Monts d'Arree- Finistere department); Origine des elements de la famille de l'uranium-235 observes dans la riviere Ellez a proximite du reacteur nucleaire experimental EL4 en cours de demantelement (Mont d'Arree - departement du Finistere). Resultats et premiers constats annee 2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    In a previous study which concerned the catchment basin of the harbour of Brest, the A.C.R.O. put in evidence a marking by artificial radioelements around the power plant of Brennilis which can be imputed without ambiguities to the nuclear installation. It also put in evidence abnormalities concerning the natural radioactivity which justifies this new study. In the area of the Monts d'Arree, actinium 227 ({sup 227}Ac), non born by its ascendents which are {sup 235}U and {sup 231}Pa is observed. This phenomenon is characterized by mass activities superior to these ones of {sup 235}U and able to reach these ones of {sup 238}U. Its presence corresponds with the drainage of the Ellez river since the former channel of radioactive effluents releases from the nuclear power plant EL-4 up to the reservoir Saint-Herblot situated 6 km downstream. The strongest values of radioactivity are registered near the disused power plant, at this place a relationship exists between the level of actinium 227 and this one of the artificial radioactivity as it exists a relationship with the decay products of radon exhaled from the subsoil ({sup 210}Pb). But its presence is not limited to a part of the Ellez river, it is equally observed in terrestrial medium, in places in priori not influenced by the direct liquid effluents of the power plant. This place is situated at more than 4 km and without any connection with the Ellez waters. At this stage of the study, it is not possible to answer with certainty the question of the origin of this phenomenon. A new reorientation is considered indispensable to clarify definitively the origin of this unknown phenomenon in the scientific publications and the environmental monitoring. (N.C.)

  11. Subcellular drug targeting, pharmacokinetics and bioavailability.

    Science.gov (United States)

    Leucuta, Sorin Emilian

    2014-02-01

    Effective treatment of diseases at the molecular level is possible by directing the drug substance (micromolecular, protein or peptide drugs, DNA, oligonucleotides, siRNA) with the aid of a specialized nanoparticulate carrier, for safe and effective transport to the specific site of action in the cytosol and its organelles including nuclear targeting. To achieve efficient cytosolic delivery of therapeutics or nuclear targeting, different drug delivery systems (DDS) have been developed (macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers) capable of subcellular internalization overcoming the biological barriers, by passive targeting and especially by active targeting (receptor-targeted delivery). The success depends on the physicochemical nature of DDS, intracellular barriers that these systems need to overcome, the bioavailability of the bioactive drug, biodistribution, the intracellular pharmacokinetics and its influence on the pharmacodynamic effect. Models necessary for this purpose exist but they need to be more developed especially with quantitative treatments, after the development of the means of highlighting the evolution of the drug substance in biophase or at the level of the target cellular organelle by quantitative assays. It is expected that intracellularly targeted drug delivery approaches will be clinically useful using specialized DDSs belonging to the pharmaceutical nanotechnologies.

  12. Hypersonic sliding target tracking in near space

    Directory of Open Access Journals (Sweden)

    Xiang-yu Zhang

    2015-12-01

    Full Text Available To improve the tracking accuracy of hypersonic sliding target in near space, the influence of target hypersonic movement on radar detection and tracking is analyzed, and an IMM tracking algorithm is proposed based on radial velocity compensating and cancellation processing of high dynamic biases under the earth centered earth fixed (ECEF coordinate. Based on the analysis of effect of target hypersonic movement, a measurement model is constructed to reduce the filter divergence which is caused by the model mismatch. The high dynamic biases due to the target hypersonic movement are approximately compensated through radial velocity estimation to achieve the hypersonic target tracking at low systematic biases in near space. The high dynamic biases are further eliminated by the cancellation processing of different radars, in which the track association problem can be solved when the dynamic biases are low. An IMM algorithm based on constant acceleration (CA, constant turning (CT and Singer models is used to achieve the hypersonic sliding target tracking in near space. Simulation results show that the target tracking in near space can be achieved more effectively by using the proposed algorithm.

  13. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  14. Improving pharmacological targeting of AKT in melanoma.

    Science.gov (United States)

    Kuzu, Omer F; Gowda, Raghavendra; Sharma, Arati; Noory, Mohammad A; Dinavahi, Saketh S; Kardos, Gregory; Drabick, Joseph J; Robertson, Gavin P

    2017-09-28

    Targeting AKT with pharmacological agents inhibiting this protein in the melanoma clinic is ineffective. This is a major contradiction considering the substantial preclinical data suggesting AKT as an effective target. Various approaches have been undertaken to unravel this contradiction and drug combinations sought that could resolve this concern. We have shown that genetic targeting AKT3 or WEE1 can be effective for inhibiting tumor growth in preclinical animal models. However, no one has examined whether combining pharmacological agents targeting each of these enzymes could be more effective than inhibiting each alone and enhance the efficacy of targeting AKT in melanoma. This report shows that combining the AKT inhibitors (AZD5363 or MK1775) with the WEE1 inhibitor, AZD5363, can synergistically kill cultured melanoma cells and decrease melanoma tumor growth by greater than 90%. Co-targeting AKT and WEE1 led to enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating the transcription factors p53 and FOXM1, as well as the proteins whose expression is regulated by these two proteins. Thus, this study identifies a unique combination of pharmacological agents and the ratio needed for efficacy that could be used to potentially improve the therapeutic effectiveness of targeting AKT in the clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. COMPASS polarized target for Drell-Yan

    CERN Document Server

    Pešek, M

    2014-01-01

    In the COMPASS Drell–Yan experiment the pion beam with momen tum of 190 GeV/ c and in- tensity up to 10 8 pions/s will interact with transversely polarized proton t arget producing muon pair via Drell–Yan process. The solid-state NH 3 will be polarized by dynamic nuclear polar- ization. Maximum polarization reached during data taking i s expected to be up to 90%. The non-interacting beam and other particles produced inside t he target will be stopped in the hadron absorber after the target. Two target cells, sepparated by a 20 cm gap in between, each 55 cm long and 4 cm in diameter give the target material volume about 691 cm 3 . The target platform needs to be moved by 2.3 m in upstream dire ction from the position used in previous experiments in order to accomodate the absorber. D uring the beam time higher radiation is expected in the area of the control room. Thus a new target r emote control system is needed. The target magnet is undergoing a substantial upgrade. Drell–Yan data taking is expected t...

  16. Systemic Targeted Alpha Radiotherapy for Cancer

    Directory of Open Access Journals (Sweden)

    Allan B. J.

    2013-09-01

    Full Text Available Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g.glioblastoma multiformeand to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. Objective: This review charts the developing role of systemic high LET, internal radiation therapy. Method: Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukemia and micrometastases, there is now evidence that solid tumors can also be regressed. Results: Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specifc cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. Conclusion: Preclinical studies and clinical trials of alpha therapy are discussed for leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

  17. Gene Therapy and Targeted Toxins for Glioma

    Science.gov (United States)

    Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

    2011-01-01

    The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

  18. Folate targeted polymeric 'green' nanotherapy for cancer

    Science.gov (United States)

    Narayanan, Sreeja; Binulal, N. S.; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

    2010-07-01

    The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)—'NanoGSE'—was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ~ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ~ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

  19. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. © 2015 WILEY Periodicals, Inc.

  20. Preliminary investigation of solid target geometry

    Energy Technology Data Exchange (ETDEWEB)

    Haga, Katsuhiro; Kaminaga, Masanori; Hino, Ryutaro; Takada, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Shafiqul, I.M.; Tsuji, Nobumasa; Okamoto, Hutoshi; Kumasaka, Katsuyuki; Hayashi, Katsumi

    1997-11-01

    In this report, we introduce the developing plan for a solid metal target structure. Supposing tantalum as the target material, the temperature distribution and the maximum thermal stress in a tantalum plate of a solid metal target was evaluated under a water cooling condition, using the heat generation rate calculated with the JAERI`s neutron transport code. The calculation results showed that the water velocity was higher than 10 m/s in order to cool the 3mm-thick target plate down to 200degC when the target surface was smooth and heat transfer rate was calculated with the Dittus-Boelter equation. In this case, the maximum thermal stress is 50 MPa at the target plate surface. The coolant water flow distribution in a target vessel was also evaluated for ISIS-type flow channels and the parallel flow channels. In the ISIS-type flow channels, at least 25mm height of the coolant plenum is needed for a uniform flow distribution. The maximum flow velocity difference between the flow gaps in the parallel flow channels was 30%. A heat transfer augmentation experiment was conducted using ribbed-surface flow channel. The heat transfer rate was confirmed to increase up to twice the value of that for a smooth surface. (author)